Final HSCM 2023 Student Notebook

2023
HIGH SCHOOL
CANCER MASTERCLASS
STUDENT NOTEBOOK
Table of Contents
Table of Contents 2
President’s Message to Students 3
NSW Directors’ Message to Students 4
Acknowledgements 5
Masterclass 1: Normal Cell Biology 6
Masterclass 2: Cancer Biology 14
Masterclass 3: Genetic Basis of Cancer 18
Masterclass 4: Environment and Cancer 23
Masterclass 5: Cancer Screening and Prevention I 26
Masterclass 6: Cancer Screening and Prevention II 33
Masterclass 7: Treatments – Introduction 39
Masterclass 8: Treatments – Applications 46
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President’s Message to Students
Dear students,
In 2022 alone, about 162,000 new cases of cancer were diagnosed in Australia, an average of over 440 every day.
Furthermore, the Australian Institute of Health and Welfare (AIHW) estimates that 1 in 2 Australians will be diagnosed with
cancer by age 85. It follows then, that cancer is almost certainly going to impact our lives or the life of someone we know; a
friend, a relative, or a loved one. Despite affecting over 1 million Australians today, there remains a distinct lack of media
coverage and public awareness of cancer. This gap is also reflected in the fact that most young Australians receive little to no
teaching about cancer during their secondary or tertiary education.
In 2015, my friends and I decided to address this glaring issue by founding the Young Australians’ Cancer Initiative
(YACI; formerly Australian Cancer & Health Sciences Competition) as a group of seven second-year biomedicine students
at the University of Melbourne. Our vision then, and today, is to empower young Australians with enriching and engaging
learning experiences about cancer, such as the High School Cancer Masterclasses (HSCM) program. We believe that it is
crucial for young people to have a fundamental understanding of what cancer is; who can get cancer; how cancer is diagnosed
and treated; and why it is important for cancer to be identified and prevented early. Through this, we aim to equip young
Australians with the ability to make healthier choices and advocate for others to do the same. In doing so, we seek to inspire
a generation of cancer-literate individuals who can contribute to the fight against cancer irrespective of their career paths.
The team at YACI are thrilled to welcome students to the Masterclasses program in 2023. In its 6th consecutive year
running, the Masterclasses program curriculum has been refreshed following feedback from last year’s participants and will
be delivered online and in-person. The Masterclasses program would not be possible without the generous contribution of our
Masterclass tutors – volunteer university students who have been selected and trained to deliver each Masterclass – as well
as high school teachers, who have played a vital role in coordinating Masterclasses for participating schools and students. We
thank you for their ongoing support of the YACI's initiatives.
For more information about YACI and our initiatives, please visit our website and follow our Facebook page for
updates. We hope that you find the 2023 Masterclasses to be an enjoyable, valuable, and stimulating learning experience
which expands your knowledge of cancer and challenges your thinking.
Best wishes,
Dr Jasun Li
YACI President 2023
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NSW Directors’ Message to Students
Dear students,
The Young Australians’ Cancer Initiative (YACI) first expanded to NSW in 2019 in the form of the High School
Cancer Symposium. YACI continued to develop new initiatives in Victoria and the HSCM was developed as a community
outreach program of the Young Australians’ Cancer Initiative in 2018 with an ambitious vision in mind. We wanted to expand
the reach of YACI’s core purpose of delivering high quality cancer science education and motivating Australia’s youth to
make positive differences to health-related behaviours in their community. The HSCM program is uniquely designed to
achieve this vision by either sending tutors out to schools or delivering tutorials through other online means, as has been
required in COVID-19 pandemic.. We strive to make our program as accessible as possible, which is justification for it being
free-to-access. We also hope that the outreach nature of our program will dismantle geographical barriers that might otherwise
prevent schools from participating in YACI’s initiatives. The provision of live teaching also means that classes can be adapted
‘on-the-go’ to the individual student cohort at each school, particularly in terms of the variety of year levels involved and
students’ prior knowledge. The other component of HSCM’s vision was to amplify the impact of YACI within the broader
community. Indeed, HSCM operates on the principle of empowering students through education and inspiration. We believe
that students play a unique role in mediating social change and influencing community discourse on health-related issues.
Following the successful pilot of the HSCM in Victoria, we soon brought the program to NSW with the vision coming
to fruition in 2022. We are very excited to continue this program in 2023 with a wider reach of schools and improved content
based on previous feedback and better adaptation to the NSW syllabus.
The HSCM program has been designed as a series of eight, thematically sequenced, interactive cancer health science
tutorials. A holistic approach to cancer education has been adopted in designing the program. In addition to basic and clinical
sciences, students will get an insight into the socioeconomic impact of cancer, pathways into cancer research, public health,
and cancer patient journeys. Volunteer tutors from a diverse range of health science academic and professional backgrounds
deliver the program to schools, guided by students’ interests and preferences for learning. An additional component to the
program is the student-initiated community engagement project, for which students are encouraged to formulate a project to
promote cancer-awareness at their school and in their local community.
We hope that students will take away from HSCM an increased understanding of advanced biological and health
science concepts, which they may not have otherwise encountered at high school. Students should be able to apply this new
knowledge to their biological studies at school but will also be better placed to engage with cancer public health initiatives
and cancer research. The outstanding tutors that deliver the HSCM program also may serve as mentors to students, providing
invaluable advice regarding tertiary study options that provide exposure to cancer sciences. Most importantly, we believe
students will have an enjoyable and personally enriching experience participating in the HSCM program.
Sincerely,
Dr Lin Yang & Mr Ashvin Bandodkar
YACI NSW Co-Directors 2023
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Acknowledgements
The content of our NSW High School Cancer Masterclass (HSCM) program in 2023 builds significantly on the
Online Syllabus as well as the previous 2021 edition of the notebooks developed by the following past members of Young
Australians’ Cancer Initiative (YACI; formerly Australian Cancer & Health Sciences Competition) whom we gratefully
acknowledge:
● Online Syllabus Team:

o Jenny Pham, Luke Thorburn, Nic Roumeliotis, Roger Zhou, Lisa Shen, John Huang, Anthony Lim
● Notebook Team:
o Masterclass 1 – Basics of Cancer Biology: Claire Livingstone, Raymond Wu
o Masterclass 2 – Causes of. Cancer: Jackie Vuong, Natalie Lim
o Masterclass 3 – Types of Cancer: Gloria Xing, Thomas Chow
o Masterclass 4 – Treatment and Prevention of Cancer: Jerry Luo, Oscar Lu
Since 2021, we have extensively reviewed the previous content materials for the HSCM program to deliver up-to-
date, scientifically accurate information to our high school students. We have also incorporated real-life examples of how this
knowledge may be relevant to high school students, focusing particularly on Human Papillomavirus (HPV), against which
vaccinations are available through the National Immunisation Program. In addition, case studies have been created to help
students synthesise the vast amount of novel information learned throughout the HSCM program and apply it to solve real-
life problems. We thank the following members who have contributed to the development of our current notebooks:
o Masterclass 1 – Basics of Cancer Biology: Isabella Papalia, Nakjun Sung

o Masterclass 2 – Causes of Cancer: Isabella Papalia, Nakjun Sung
o Masterclass 3 – Cancer Screening and Prevention: Jonathan He
o Masterclass 4 – Treatment of Cancer: Nakjun Sung
o Cover page design: Wendy Lin
Lastly, we thank the NSW Co-Directors, Lin Yang & Ashvin Bandodkar, as well as the coordinators of HSCM
program, Keshini Vijayan and Shawn Yang who have provided us with thoughtful and valuable feedback and encouragement
throughout the process of content development.
Amy Tsoi & Afra Kamal
YACI NSW Content Officers 2023
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Masterclass 1: Normal Cell Biology
Learning objectives
● To understand different components of a mammalian cell and their functions

● To understand the structure of DNA and how their nucleotide patterns code for amino acids
● To understand the processes involved in the formation of proteins: DNA transcription and RNA translation
● To understand the different phases of the cell cycle
● To understand the cell signalling cascade necessary for cell replication
● To gain an understanding of the basic immunological response
In the Biology Syllabus
● Module 5: Heredity
o DNA and Polypeptide Synthesis:
▪ Model the processes of polypeptide synthesis
● Module 7: Infectious Disease
o Immunity
▪ Investigate and model the innate and adaptive immune systems in the body
Section 1: Introduction to cells
Cells and cancer
Definition of cancer: a group of diseases that are caused by abnormal cells that grow uncontrollably due to genetic abnormalities.
When cells become abnormal, they can grow out of control and make copies of themselves too quickly, leading to the group of
diseases we call cancer. Therefore, to understand cancer, we need to understand normal cell biology.
Cells
In the biological realm, all living entities are made of cells, which are the building blocks of our bodies. These building blocks,
enclosed by thin membranes, contain a water-rich solution of chemicals and cellular machineries that carry out various functions
of life. These cells cluster together into various functional groups called tissues (see Figure 1-1). Organs are formed by several
groups of tissues.
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Figure 1-1. The four main types of tissues. Adapted from: https://philschatz.com/anatomy-book/contents/m46046.html
Organelles
The cells that make up our bodies contain cellular machineries called organelles (see Figure 1-2). They each carry out unique
roles that allow the cell to perform tasks that are necessary for life (and death).
Figure 1-2. A cell and its organelles. Adapted from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/organelle
● The nucleus: houses the cell’s genetic material in the form of a chemical structure called DNA (deoxyribonucleic acid)
and controls the cell’s growth, reproduction and activity.
● Continuous with the nucleus, there are two types of endoplasmic reticulum (ER): rough and smooth.
o The rough endoplasmic reticulum is studded with structures called ribosomes that are responsible for protein
synthesis.
o In contrast, smooth endoplasmic reticulum lacks ribosomes and is responsible for lipid synthesis and
detoxification of various substances.
● The lysosome is the cell’s waste removal and digestive system
● Mitochondria are the main sites of the cell’s energy production.
● Golgi apparatus is a series of flattened stacks where proteins are packaged, modified and sorted for use in other parts of
the cell.
● And all these organelles as well as the cell’s biochemical molecules are in the aqueous solution called cytosol.
● Everything inside the cell membrane excluding the nucleus and its content is known as cytoplasm.
In the nucleus: DNA
● All 37.2 trillion cells comprising a human body originates from one single cell.
● This cell continuously divides in early life to make clones of itself.
● These clones then specialise into certain types of cells (i.e., epithelial, connective, muscular, nervous cells)
But how can a single cell, spontaneously become an entire human body?
All nuclei of cells contain DNA, which is a molecule that provides instructional template for the cell to produce functional
molecules such as proteins. Most of the somatic cells (all the cells besides the reproductive cells), usually contain the same DNA.
When cells are dividing, the DNA becomes packed into 23 pairs of structures called chromosomes (see Figure 1-3).
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Figure 1-3. The structure of DNA and nucleotides. Adapted from:
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dna
If we look closer at the DNA chromosomes on Figure 1-3, they are comprised of units called nucleosomes, which are made of
structural proteins called histones around which the DNA molecules are wrapped. The DNA itself has two strands of DNA
molecules that intertwine each other to form a double-stranded helix. Each DNA strand is a sequence of repeating units known
as nucleotides. A nucleotide is a chemical molecule that has three components: a sugar molecule, a phosphate group and a
nitrogenous base. The nitrogenous bases that are used for the synthesis of DNA are guanine (G), cytosine (C), adenine (A) and
thymine (T). These nucleotides on each strand connect with those of the other strand by the complementary pairing of the
nitrogenous bases (i.e., G only connects with C while A only connects with T).
The central dogma
The genetic information is like a blueprint for how cells should live. However, the blueprint itself does not carry out the function.
It has to be read by workers to produce certain products that can carry out their functions. However, it would be inefficient to read
out the whole blueprint each time a certain product has to be made; therefore, only a small part of the blueprint can be transcribed
onto a piece of paper that can be read by the workers. In cellular terms, the workers are enzymes, or proteins that have biological
roles, and the products are usually proteins including the enzymes. And the transcribed version of the blueprint is called RNA
(ribonucleic acid). RNA is slightly different from DNA in that it is single-stranded, and its nucleotides have subtle differences
compared to those of DNA. Also, while the use of G, C and A nitrogenous bases are the same, the uracil (T) base is used instead
of T.
The process by which a protein is made from the instructions encoded genes is the central dogma of life (see Figure 1-4).
The stages of this process are:
1. Transcription: When the cell is required to make a protein, an enzyme called RNA polymerase unwinds the DNA
molecule, at the point where the gene’s sequence begins. RNA polymerase uses only one strand on DNA as a template to
synthesise another molecule, messenger RNA (mRNA), which has the complementary base pairs to the template.
2. Modification of the mRNA: The molecule is capped at one end, and some segments are cut out. Also, a tail of repeated
adenosine (A) nucleotides may be added at the other end to increase stability. The mRNA is then exported out of the
nucleus into the cytoplasm.
3. Translation: Ribosomes in the cytoplasm bind to the mRNA. The ribosome recruits transfer molecules, transfer RNA
(tRNA), which carry amino acids that are required to make the protein. The sequence of three base pairs on the mRNA (a
copy of the DNA), encode for a specific amino acid. The ribosome joins these amino acids together to make a protein,
and this is called translation.
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Figure 1-4. The central dogma of molecular biology.
Section 2: The life of a cell
As living entities, cells are dynamic. For a cell to replicate and divide, it must undergo a sequence of steps that is known as the
cell cycle (see Figure 1-5). This cell cycle allows a cell to make a copy of its DNA and divide it into two identical daughter cells.
The cell cycle
Figure 1-5. The cell cycle.

G1: Interphase: Gap 1
During the first gap phase (G1), cells not only grow and synthesise proteins as well as organelles necessary for the later cell cycle
progression, but they also keep checking whether the cell and its outer environment is fit for the cell division or not. Once the cell
completes the G1 phase, it commits to progressing through the cell cycle and begins to duplicate its DNA.
S: Interphase: Synthesis
The cell replicates its DNA in the S phase (S for DNA Synthesis). Once complete, there will be two identical copies of the cell’s
DNA.
G2: Interphase: Gap 2

The cell continues to grow while checking whether its environment is fit for division. In addition, the cell checks for any errors in
DNA replication during the S phase. Once the cell is ready, it will progress into the division process called mitosis.
M: Dividing: Mitosis
The process of dividing is in several stages. Once divided, there are now two ‘daughter’ cells that contain identical genetic
information.
It is worth noting that certain types of cells undergo the cell cycle more often than others. For example, our skin cells are
constantly exposed to the environment and become damaged frequently. To replace the damaged cells, skin cells continuously
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replicate and divide. Other types of cells that go through the cell cycle frequently include hair cells, blood cells and cells in the
gastrointestinal tract.
G0: Resting: Quiescence
Some cells remain in a resting state known as G0 phase. Sometimes, these cells may gain signals to grow and progress through the
cell cycle. However, many types of cells such as nerve cells remain permanently in this phase, thus lacking regenerative capacity.
Cell signalling
Because a human body is composed of many types of cells that are in a delicate balance, cells cannot continuously replicate and
divide all the time. Then how does a cell know when to progress through the cell cycle? The answer is via biochemical signals.
From the beginning to the end, cells of a human body are constantly exposed to a myriad of signals from one another and outside
of the body. Via these signals, the cells communicate and regulate the activity of one another. Some of these signals may instruct a
cell to grow, proliferate (replicate and divide), move around, contract, or even die. The following steps describe the basic
signalling process required for initiating the cell cycle:
1. Reception: A signalling molecule known as a ‘growth factor’ binds to its specific receptor protein on the surface of the
target cell. The receptor protein then undergoes a slight change in its shape that initiates the relay of the growth signal.
2. Transduction: Once the receptor is activated via the change in its shape, it, in turn, activates other signalling pathways
that are inside the cell. These pathways are known as ‘intracellular signalling pathways’. The intracellular signalling
pathways involve series of intracellular signalling proteins that activate one another in a cascade.
3. Cellular response: At the end of the cascade above, the signals finally act on effector proteins that perform certain roles
to change the behaviour of the cell. For example, a signal reaching the nucleus may alter the expression of a gene and
lead to the production of a protein. In another case, a signal may act on an enzyme to increase or decrease its activity
level.
Errors in the DNA and their consequences
The human genome (collection of all genetic material in an organism) contains approximately three billion pairs of nucleotides.
Given this number and the number of times that human cells have to divide throughout a person’s life, it is conceivable that errors
may occur.
Masterclass 1 questions
Question 1
What happens when errors occur in DNA replication? Consider the Central Dogma of Life.
DNA damage can also occur because of external factors, such as exposure to UV light, infection, ionising radiation and certain
chemicals (called carcinogens). Damage to the DNA is detected by proofreading mechanisms (e.g., DNA polymerases) and in
response, the body tries to control the damage. The body tries to stop the cell from dividing and repair the DNA via various repair
mechanisms by using enzymes that cut out damaged segments. From here there is generally three outcomes:
1. Successful repair, and the cell returns to the cell cycle

2. Extensive damage (i.e., the DNA is so damaged that the repair mechanisms can’t fix them) results in apoptosis, which is
where the cell is ordered to commit suicide.
3. Failed repair and accumulation of damage – results in cancer
Section 3: Basics of immunology
The immune system is our bodies’ defence system. It involves various organs, tissues, cells and chemical substances to protect our
bodies from foreign harms. One of the major roles performed by the immune system is fighting against infectious agents such as
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bacteria, viruses, fungi and parasites. Besides, it can also recognise cancer cells and destroy them. Therefore, it is important to
gain a basic understanding of the immune system.
There are two arms of the immune system in the human body: innate and adaptive (see Figure 1-6). The innate immune system
is involved in the immediate responses against any immunological insults (for example, from bacteria). It includes:
● 1st line defence

o This is composed of physical (e.g., skin), chemical (e.g. substances in our tears) and mechanical barriers (e.g.
our airways can move mucous that traps infectious organisms up and out of the airways) that prevent the entry
of pathogens (agents that can cause diseases, including infectious microorganisms) into the cells. An example
of this is the skin, which forms a physical barrier against various microorganisms that are in the environment.
● nd
2 line defence
o The second line of defence involves some of the white blood cells (also known as leukocytes) such as
neutrophils and macrophages. These cells can recognise and destroy pathogens by engulfing and digesting
them through a process called phagocytosis (derived from Greek prefix phago-, meaning ‘to eat’). Some of
these white blood cells are responsible for the creamy white fluid we call pus, which develops in infected cuts or
pimples, for example.
Figure 1-6. The overview of the immune system. The immune system can be divided into innate and adaptive components.
The adaptive immune system, on the other hand, allows for a more specific response. It receives the information regarding the
pathogen and generates or orchestrates the immune response that is tailored against that specific pathogen. This tailoring process,
compared to the non-specific and immediate action of the innate immune system, takes longer in time. However, it is
advantageous because it can generate a memory of that particular immune response and initiate a quicker and stronger attack
against the pathogen in its subsequent encounters. While the field of the immune system is very complex, a few important
components of the adaptive immune system relevant for cancer are listed below:
Figure 1-7. Types of lymphocytes. When activated, B cells specialise into plasma cells that release antibodies into the blood. T
cells can be classified into two types: helper T cells and cytotoxic T cells.
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B lymphocytes
B lymphocytes (or B cells) are one type of cells involved in the adaptive immune system. Each B cell can recognise a specific
molecule (known as the antigen) expressed by pathogens or cancer cells. Antigens are parts of pathogens such as infectious
organisms and cancer cells that white blood cells can recognise. When the B cell sees the antigen, it becomes activated and begins
to proliferate. Some of these B cells become specialised into plasma cells that produce immune proteins called antibodies (see
below). Some become memory B cells that remember the encounter with the antigen; and when the body is exposed to the same
antigen again, the memory B cells become activated and provide quicker and stronger immune responses against the pathogens
that contain the antigen.
Each of B cells produces antibodies with a unique specificity against a certain antigen. And the antibodies produced by many B
cells can target a wide repertoire of antigens to perform various roles. For example, antibodies that bind to antigens on viruses can
prevent them from entering our cells. Antibodies, when bound to antigens on the surface of pathogens such as bacteria, can ‘flag’
the bacteria so that the cells of the innate immune system can better recognise and destroy them.
T lymphocytes
T lymphocytes (or T cells) are another type of adaptive immune cells. Broadly, T lymphocytes are classified into two types:
● Helper T cells
o Helper T cells are like the conductor of an orchestra. When they recognise a specific part of a proteinaceous
antigen, they orchestrate both the innate and adaptive immune system to mount an attack against the pathogens
that harbour the antigen. They perform this role by releasing signalling molecules that recruit other immune
cells and giving them ‘help’.
● Cytotoxic T cells
o Cytotoxic T cells, as their names suggest, are directly toxic against their target cells. When they recognise a part
of an antigen and become activated, they come in direct contact with the cells or pathogens expressing that
antigen on their surface. Once the cytotoxic T cells see the antigen, they release toxic chemicals into the target
cells and directly kill them by inducing apoptosis.
References
1. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, et al. Molecular Biology of the cell. 6 th ed. New York:
Garland Science; 2014.
2. Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei Raffaella, Frabetti F, et al. An estimation of the number of cells
in the human body. Ann Hum Biol. 2013 Nov-Dec;40(6):463-71.
3. Kenneth M, Casey W. Janeway’s immunobiology. 9th ed. New York: Garland Science; 2016.
4. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 7 th ed. New York: WH Freeman and Company; 2016.
5. Strachan T, Read AP. Human Molecular Genetics. 5th ed. New York: Garland Science; 2018.
6. Watson JD, Crick FHC. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953
Apr;171(4356):737-8.
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Masterclass 2: Cancer Biology
Learning objectives
● To understand the terms ‘cancer and ‘tumour’

● To differentiate between ‘benign’ and ‘malignant’ tumours
● To gain an appreciation for the hallmarks of cancer
● To understand the two models of cancer progression and how they differ
● Module 6: Genetic Change

o Mutation
▪ Compare the causes, processes and effects of different types of mutation
▪ Assess the significance of ‘coding’ and ‘non-coding’ DNA segments in the process of mutation
Section 1: Basics of cancer biology
Cancer is an evolutionary process occurring at the level of cells. In a cancerous cell, the genetic errors, known as mutations,
confers a survival advantage for the cell. From the perspective of this cell that wants to grow, replicate and divide, the mutations
are advantageous. However, the perspective of a cancerous cell does not equal the perspective of the entire human body. The
survival advantage conferred to the individual cell may be disadvantageous for the survival of the organism as a whole.
Figure 2-1. A simple illustration of how cancer progresses. Adapted from: https://www.cancervic.org.au/cancer-
information/what-is-cancer
As a cell becomes rogue due to the mutations, it begins to proliferate to form a lump of cells called tumours (derived from Latin
word tumere, meaning ‘to swell’). Not all tumours are cancerous, however. The two broad types of tumours are described below:
● Benign tumours are localised to tissues, meaning that they are confined to one area and do not spread to other areas
around the body.
● Malignant tumours contain cells that can invade the lymph or the bloodstream. They then use these vessels to travel to
other parts of the body and form secondary tumours in different tissues. Malignant tumours are known as cancers.
(Note: some benign tumours can become malignant.)
However, cancers can take many forms. To describe commonalities that exist between these many forms of cancer, Hanahan and
Weinberg have published a seminal paper that explains the ‘hallmarks of cancer’ (see Figure 2-2).
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Hallmarks of cancer
Figure 2-2. The hallmarks of cancer. Adapted from: Cell 2011 144646-674DOI: (10.1016/j.cell.2011.02.013)
1. Sustaining proliferative signalling

● Cancer cells can grow and divide without signals. An example of how this occurs is through a mutation in Ras
protein, a protein that promotes cell proliferation when it is activated. Ras is normally active for only a short
period of time. A mutation in the DNA encoding for this protein allows it to remain active, accelerating growth
signalling cascades.
2. Evading growth suppressors
● Overgrowth of normal cells is prevented through inhibitory signals which prevent the cell from going into the
synthesis phase of the cell cycle. The retinoblastoma protein (Rb) is one of these inhibitory proteins. If the gene
encoding this protein becomes faulty, the inhibitory signal that stops the cell from dividing is lost. Therefore, the
cell continues to replicate and divide.
3. Resisting cell death
● When the DNA is damaged beyond the cell’s capacity to repair, apoptosis is induced by a protein called p53,
often referred to as the ‘guardian of the genome’. When the gene encoding for p53 is mutated, p53 cannot
recognise the DNA errors. Thus, the cell can escape apoptosis. This gene is mutated in over 50% of cancers.
4. Enabling replicative immortality
● Normal cells can only divide a limited number of times. This is because of telomeres attached to the tips of the
chromosomes. After each division, the length of telomeres shortens; and after a certain point, the cell can no
longer divide. However, cancerous cells can reactivate an enzyme that adds on telomeres called telomerase to
allow themselves to replicate infinitely.
5. Inducing angiogenesis
● Angiogenesis is the process by which new blood vessels are formed. Because cancer cells are continuously
growing and dividing, they require a significant amount of energy that has to be made from the nutrients and
oxygen. Therefore, cancer cells release signals known as vascular endothelial growth factor (VEGF) to recruit
blood vessels from their surroundings. Consequently, new blood vessels form around the cancer cells to deliver
them nutrients and oxygen.
6. Activating invasion and metastasis
● Many cells in our bodies are physically connected to each other. However, cancer cells that have mutations in
proteins that make up these intercellular connections can break away from other cells to invade into its
environment. As these cells move around the surrounding environment, they may reach blood vessels or
lymphatic vessels (which drain fluid from tissues and circulate it back into the blood) to spread into a distant site
in the body. This process of invading into a distant body site is called metastasis.
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7. Genome instability and mutation
● As cancer cells keep proliferating, they start to accumulate mutations over time. And a critical point is reached
when the cancer cell possesses a mutation in the DNA regions that code for DNA repair enzymes. If these repair
enzymes become dysfunctional, then the cancer cells start to accumulate DNA mutations at a faster rate, and the
cancer cell genome becomes unstable.
8. Tumour-promoting inflammation
● Tumours are known to create a pro-inflammatory environment by surrounding themselves with immune cells.
Paradoxically, this environment may increase the availability of factors that promote cancer cell growth,
angiogenesis, invasion, and metastasis.
9. Deregulating cellular energetics
● Cancer cells switch their metabolism from aerobic respiration to glycolysis (known as the 'Warburg
Hypothesis'). Aerobic respiration is the means of producing energy more efficiently compared to glycolysis
alone. Therefore, it may seem counterintuitive that hyperactive cancer cells metabolically switch from aerobic
respiration to glycolysis. While there is an undoing research in this aspect, it seems that the switch allows cancer
cells to gain more intermediate metabolites and nutrients that are necessary for their growth.
10. Avoiding immune destruction
● The theory of immune surveillance states that there is an ongoing monitoring of our normal cells by the immune
system to prevent cancer development. However, some cancer cells can express proteins that inhibit their
immune recognition and destruction.
These characteristics of cancer are widely applicable across many cancer types and have allowed for improvements in devising
out treatment plans for cancer.
Section 2: Models of cancer progression
There are different ‘models’ of cancer progression depending on the cell type that is involved in cancer formation.
Linear progression model
Figure 2-3. Linear progression model of cancer. Cancer cells acquire mutations in a stepwise manner and become increasingly
aggressive over time.
The linear progression model of cancer states that mutations in cancer cells occur in a stepwise manner. Following the acquisition
of mutations, some of the cancer cells that are better ‘fit’ to survive in the given environment are selected and continue to
proliferate at the primary tumour site. After round of mutations that make cancer cells more aggressive over time, the
dissemination or metastasis of a fully malignant cell occurs at a distant site of the body from the primary tumour.
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Parallel progression model
Figure 2-4. Parallel progression model of cancer. In this model, the dissemination of metastatic cancer cells occurs early in the
progression of cancer. These early metastatic deposits and the primary tumour grow in parallel at different rates.
The parallel progression model is similar to linear progression model in the idea that cancer cells are selected for their fitness to
survive in their given environments. However, in this model, the dissemination of cancer cells occurs early before the primary
tumour fully develops. As a result, the early metastatic deposits and the primary tumour grow and evolve in parallel at different
rates. In contrast to the linear progression model (see Figure 2-3), this model allows for greater diversity between the metastatic
deposits and the primary tumour.
References
1. Cancer Council Victoria. What is cancer? [Internet]. Melbourne (VIC): Cancer Council Victoria; 2021 [updated 2021;
cited 2021 May 14]. Available from: https://www.cancervic.org.au/cancer-information/what-is-cancer
2. Hanahan D, Weinberg RA. Hallmarks of cancer. Cell. 2000 Jan;100(1):57-70.
3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar;144(5):646-74.
4. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer. 2009 Apr;9(4):302-12.
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Masterclass 3: Genetic Basis of Cancer
Learning objectives
● To gain knowledge of the types of genetic mutations

● To appreciate the importance of genetic mutations in cancer formation
● To understand the role of oncogenes and tumour suppressor genes in cancer development
● Module 6: Heredity
o Mutation
▪ Compare the causes, processes and effects of different types of mutation
▪ Assess the significance of ‘coding’ and ‘non-coding’ DNA segments in the process of mutation
Revision
● Cancer is a disease caused by genetic mutations (or errors in the instructions of the cells). Errors in the genetic code
cause cells to behave abnormally to grow and divide uncontrollably.
● As we discussed in the first lesson, DNA damage, in the form of mutations, can lead to changes in the proteins in the cell
to cause changes in cell behaviour. The common behaviours of cancer cells are known as the ‘hallmarks of cancer’.
In this masterclass, we will have a further look at the types of mutations and how they arise in cancer cells.
Section 1: Mutations
What is a mutation?
A mutation is like a change of a word in a sentence. A mutation is a change in the nucleotide sequence along a DNA strand
(recall the nucleotide from the last session, the basic unit of the DNA strand, the rung in the ladder). Carcinogens are substances
or other exposures that cause or promote cancer. For example, harmful products in cigarettes contain carcinogens. Mutations in
DNA can be triggered by carcinogens, in which case carcinogens are considered to be acting as mutagens (i.e., exposures that
cause mutations). The effect of a mutation depends on where it occurs, sometimes a change of a word in a sentence can still make
sense, and sometimes it changes the meaning entirely! When a mutation changes the DNA code, it changes the protein that will be
made from the transcription and translation of that code. If this change in the code occurs in an area (a gene) that encodes for
essential proteins, there is likely to be a harmful impact on the function of that protein. There are different types of mutations, and
their effects depend on where they are on the DNA strand, how big they are (how much of the sequence is changed), and whether
it can escape identification and destruction repair. The different types of mutations are explained below.
Types of mutations
1. Point mutation (see Figure 3-1)

Single nucleotide polymorphism (SNP) - aptly named point mutation - only one nucleotide is mutated.
Figure 3-1. Types of point mutations. Adapted from: https://en.wikipedia.org/wiki/Point_mutation#/media/File:Point_mutations-

en.png
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● Silent: The nucleotide that is mutated, does not cause a change in the protein made. Therefore, it does not affect
the function of the protein and the behaviour of the cell.
● Missense: The nucleotide that is mutated causes a change in the amino acid code within the protein.
Consequently, the protein may not be able to perform its normal function. However, most of the other amino
acid sequence of the protein is preserved.
● Nonsense: The mutation forms an early STOP codon before where the STOP codon is supposed to be in a
normal gene. When this codon is read by the ribosome, it stops adding on amino acids to the protein that is
being made. Therefore, protein production is incomplete, and the resultant protein becomes truncated.
2. Frame-shift mutation (see Figure 3-2)
The DNA strand can also be mutated by:
● Deletion of nucleotides
● Insertion of nucleotides
Figure 3-2. Frameshift mutations due to insertion or deletion of a nucleotide. Adapted from:
https://www.yourgenome.org/facts/what-types-of-mutation-are-there
These mutations cause an overall shift in the DNA frame being read. Therefore, these are called frame-shift mutations.
3. Chromosomal mutations
We are not going to discuss chromosomal mutations further here, but mutations can occur as ‘translocations’ between
chromosomes. In this type of mutation, a part of one chromosome breaks and become relocated onto another
chromosome.
Question 1
The original sentence: PET THE DOG AND PAY THE MAN
What type of mutations of the sentence above are seen in the following examples?
PET THE DOG FAN…
...DOG AND PAT...
PET THE DOG END...
PAT THE DOG...
Effects of mutations
As we have described, not all mutations have the same effect. It depends on the change in the protein made and the flow-on
consequences of the protein change. When the mutation causes a similar amino acid to be formed, the protein structure does not
change much, and this is called a conservative mutation. When the mutation causes the structure of the protein to change
considerably, it is called a non-conservative mutation.
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Section 2: Genes mutated in cancer
Tumour suppressor genes (TSGs)
Tumour suppressor genes are important for regulating the way cells behave. They stop cells from replicating excessively, repair
damaged DNA and cause the cell to self-destruct if the DNA is damaged beyond the cell’s capacity to repair. Remember that
genes exist in two copies (i.e., one allele each on each of two chromosomes).
● The two-hit model:
o For the function of TSGs to be completely stopped, the mutation must occur in BOTH copies. (There are
exceptions to this rule. For example, a mutation on one allele can cause the development of cancer. This is
called haploinsufficiency mutation.)
▪ The first mutation may be inherited from the parents or acquired during life.
▪ The second mutation: almost always acquired during life.
o So, someone born with one mutated gene is more likely to develop cancer as they only need one more hit for the
full knock-out of the gene's function
Figure 3-3. The two-hit model of tumour suppressor genes.

Example: TP53 as a TSG
● If a cell detects damage to its DNA, p53 protein translated from the TP53 gene puts a halt on replication to allow for
DNA repair.
● If the DNA cannot be repaired, p53 protein induces apoptosis, a programmed cell suicide system.
● This gene is one of the most mutated genes in human cancers. When its function is lost, cells can grow and divide
uncontrollably despite the significant damage taken by the DNA.
Oncogenes
An oncogene is a mutated form of a normal gene, known as a proto-oncogene, which is involved in normal cell growth. When
mutated, the oncogene causes cells to divide uncontrollably to form tumours. The mutations that cause proto-oncogenes to
become oncogenes can be inherited or caused by exposure to carcinogens. Typically, a mutation in only one copy of the gene is
required to have a cancer-promoting effect.
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Figure 3-4. One copy of proto-oncogene can become mutated into an oncogene that promotes cancer development.
Example: Ras and Myc as oncogenes

● Ras mutation makes cells resistant to ‘off’ signals → cells constantly replicating and entering the cell cycle → tumour
formation
Case Study: Genes involved in Breast Cancer
Question 1
What is the HER2 gene?
Question 2
What is the BRCA genes?
Question 3
Why does understanding the genes involved in breast cancer matter?
References
1. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, et al. Molecular Biology of the cell. 6 th ed. New York:
Garland Science; 2014.
2. Chial H. Genetic regulation of cancer. Nat Ed [Internet]. 2008 [cited 2021 Apr 11];1(1):67. Available from:
https://www.nature.com/scitable/topicpage/genetic-regulation-of-cancer-891/
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3. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971 Apr;68(4):820-
3.
4. Lin, K., Baritaki, S., Vivarelli, S., Falzone, L., Scalisi, A., Libra, M., & Bonavida, B. (2022). The Breast Cancer
Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis. Antioxidants (Basel,
Switzerland), 11(6), 1195. https://doi.org/10.3390/antiox11061195
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Masterclass 4: Environment and Cancer
Learning objectives
● To distinguish between ‘cause’ and ‘risk factor’

● To appreciate different examples of risk factors for cancer development
● Module 8: Non-Infectious Diseases and Disorders

o Causes and Effect
▪ Investigate the causes and effects of non-infectious diseases in humans
Section 1: Lifestyle, environment and cancer
Most cancers are formed due to mutations that are not inherited (i.e., acquired throughout life). Then what factors during one’s life
can lead to the development of cancer? This section explores several lifestyle and environmental factors that have been linked to
cancer development (see Figure 4-1).
Question 1
How is a risk factor different from a cause?
Figure 4-1. The percentage of cancer cases attributable to various factors that are associated with an increased risk of cancer
development. Adapted from: American Association for Cancer Research (AACR) Cancer Progress Report 2020;
https://cancerprogressreport.aacr.org/progress/cpr20-contents/cpr20-preventing-cancer-identifying-risk-factors/
Smoking
As we know, tobacco smoke contains carcinogens that can cause mutations in the cells that line the oral cavity and the respiratory
tract. It is the most important preventable risk factor for cancer development and is responsible for 20% of cancer deaths in
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Australia and 80% of lung cancers. It leads to more cancer deaths than other risk factors. Smoking causes cancer of tongue,
mouth, throat, nose, nasal sinus, voice box, oesophagus, pancreas, stomach, liver, kidney, bladder, ureter, bowel, cervix, ovary,
and bone marrow (myeloid leukaemia).
Metabolic risk factors
Metabolic risk factors including overweight, obesity, physical inactivity, and unhealthy diet are all associated with an increased
risk of cancer. There are many complex but well-studied mechanisms that link obesity to the development of cancer. Some of
these mechanisms are linked to an increased amount of fat cells that produce tumour-promoting factors such as oestrogen and
inflammatory signals. Some of the cancer types associated with these metabolic risk factors include stomach cancer, kidney
cancer, colorectal cancer, breast cancer, endometrial cancer and many more. This is particularly concerning because there is an
increasing prevalence of obesity globally. Encouraging the avoidance of these risk factors is highly recommended for patients who
are at risk of developing cancer or already suffering from cancer.
Alcohol
Alcohol is also associated with an increased risk of cancer. There is a clear relationship between the amount of alcohol the person
drinks and the amount of increase in the risk of cancer development. Among the few proposed mechanisms of how alcohol
increases the risk of cancer, the production of acetaldehyde from metabolising (breaking down) alcohol is known to be damaging
to DNA and proteins. Consumption of alcohol is associated with the development of many types of cancer – head and neck,
oesophageal, breast, colorectal, liver and stomach cancers.
Radiation
What kinds of radiation are there?

● Sun: UV radiation
● Atomic Bombs: ionising radiation
● Nuclear reactors: gamma rays
● Medical imaging: x-rays, CT scans, PET scans
How does radiation cause cancer?
● Waves of radiation can penetrate the body, cause atoms to break down and DNA to be damaged → mutations →
cancer
● For example, melanoma forms in the skin from UV radiation and can spread to elsewhere in the body.
o The use of sunscreen can reduce the risk of skin cancer.
▪ Sunscreen contains minerals or chemicals that either reflect or absorb UV radiation before it reaches
the skin
▪ SPF measures how well the sunscreen protects the skin from sunburn
● The higher the number, the more protection
● SPF30 blocks out 96.7% of UVB
● SPF50+ blocks out 98% of UVB (marginally better than above but still recommended)
Cured meat
The exact mechanism by which cured meat increases the risk of cancer development is unknown; however, it could be related to
preservative/nitrogenous compounds that promote tumour growth. Also, when an iron-containing chemical called haem is broken
down in the gut, certain chemicals known as N-nitroso compounds are formed. These chemicals can damage the cells that line the
bowel. It has been shown that eating cured meat has a clear link to the development of colorectal cancer.
Asbestos
Why is asbestos harmful?

These very small fibres can enter the lungs are remain trapped due to their structure. However, the immune system is not very
competent at removing these fibres. Therefore, the immune system attempts to increase the level of inflammation (our body’s
normal attempt to clear infections and heal damaged tissues) around the area in which asbestos is trapped in the lungs. However,
as the immune system fails to clear the fibres, the inflammation continues. This chronic inflammation can produce chemicals that
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promote cancer cell growth and proliferation. In addition, the immune cells involved in the chronic inflammation can release
chemicals that can react with DNA molecules and produce mutations.
Asbestos was once everywhere because it is a very useful compound (insulative and durable) for buildings. However, in a famous
mine (Wittenoom, WA), 7000 miners were employed during the 1950s and 60s. After its closure, there have since been 85 deaths
due to asbestosis causing pleural and peritoneal mesothelioma (cancer of the lining of the lungs and abdomen).
Infections
According to the American Cancer Society, infections are linked to about 15-20% of cancers globally (note, this may be lower in
developed countries such as United States and Australia because certain infections are less common in these countries). There are
various ways in which infections can increase the risk of cancer. Some viruses such as human papilloma virus (HPV) can affect
proteins that regulate the growth of cells and cause them to grow uncontrollably (refer to Masterclass 3). Some viruses can
incorporate their DNA molecules into human DNA to interrupt the sequence of normal gene that regulates the growth of cells. In
another example, human immunodeficiency virus (HIV) can suppress the immune system by attacking helper T cells (refer to
Masterclass 1). The loss of function of helper T cells leads to decreased level of cancer surveillance by the immune system, and
an untreated HIV infection has been linked to the development of a particular type of cancer known as Kaposi sarcoma. Infection
with Helicobacter pylori (H. pylori) bacteria has also been linked to an increased risk of stomach cancer. Since the discovery of H.
pylori by two Australian researchers, Barry Marshall and Robin Warren, it has been shown to cause chronic inflammation in the
stomach and lead to stomach cancer development.
References
1. Cancer Council. About suncscreen [Internet]. Canberra, ACT: Cancer Council; 2021 [cited 2021 Jun 7]. Available from:
https://www.cancer.org.au/cancer-information/causes-and-prevention/sun-safety/about-sunscreen
2. Cancer Council. Risk factors [Internet]. Canberra, ACT: Cancer Council; 2021 [cited 2021 Jun 7]. Available from:
https://www.cancer.org.au/about-us/policy-and-advocacy/prevention-policy/risk-factors
3. National Cancer Institute. Risk factors for cancer [Internet]. Bethesda, MD: National Cancer Institute; 2015 [cited 2021
Feb 7]. Available from: https://www.cancer.gov/about-cancer/causes-prevention/risk
4. The American Association for Cancer Research. AACR cancer progress report 2020. [Internet] Philadelphia, PA: The
American Association for Cancer Research; 2020 [cited 2021 Jan 19]. Available from:
https://cancerprogressreport.aacr.org/wp-content/uploads/sites/2/2020/09/AACR_CPR_2020.pdf
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Masterclass 5: Cancer Screening and Prevention I
Learning objectives
● To understand why we screen for cancers

● To understand the advantages of prevention over treatment
● HPV Case study
o To describe what HPV is and how it causes cancer
o To understand how HPV can be prevented
o To learn about cervical cancer and its prevention
● Module 7: Infectious Diseases

o Prevention, Treatment and Control
▪ Investigate procedures that can be employed to prevent the spread of disease, including vaccination and
public health campaigns
● Module 8: Non-infectious Disease and Disorders
o Epidemiology
▪ Analyse patterns of non-infectious diseases in populations, including their incidence and prevalence
▪ Investigate the treatment/management, and possible future directions for further research, of a non-
infectious disease
o Prevention
▪ Use secondary sources to evaluate the effectiveness of current disease-prevention methods and develop
strategies for the prevention of a non-infectious disease
Section 1: Principles of screening and prevention
Cancer screening – what is it and why do we do it?
A cancer screen is a test that checks the body for any signs of cancer before a person shows any symptoms. Though each
screening test is performed differently, they share the same goal – to detect signs of cancer earlier on, when treatment is likely to
work more effectively, resulting in better patient outcomes. Screening is thus important to reduce the morbidity and mortality
from cancer. Screening can also be cost-effective. A good screening test must change disease outcomes (i.e., improve survival
rates or reduce the morbidity of a disease).
World Health Organisation (WHO) – Features of a good screening test

● The condition/disease should be an important health problem
● There should be a recognisable early stage of the disease
● A good understanding of the natural history of the condition should exist
● An accepted treatment for patients with the disease
● A suitable test that has a high level of accuracy
● The test should be acceptable to the population
● An agreed policy on who to treat should exist
● Facilities for diagnosis & treatment need to be available
● The cost of screening should be economically balanced to the medical care otherwise required if screening didn’t exist
● Screening should be a continuing process
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Sensitivity and specificity
Figure 5-1. Sensitivity and specificity
Cancer Prevention
Cancer can be a preventable disease – one third of all cancers are preventable. Simple lifestyle changes can reduce the risk of
developing cancer.
Lifestyle changes include:

● Limiting alcohol intake
● Maintaining a healthy weight
● Eating a healthy diet
● Being sun smart
● Quitting smoking
● Being physically active
Question 1
In your own words, describe the differences between the sensitivity and specificity of a screening test.
Question 2
Define the word symptom and provide an example of a symptom you would expect to find in a cancer patient.
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Section 2: HPV case study
Human Papilloma Virus
Human Papilloma Virus (HPV) (see Figure 5-2) is a small double-stranded DNA virus that infects & replicates in the skin to
produce warts. On occasion, the virus can produce cancers. There are >100 different genotypes of HPV, with 4 main groups
infecting humans. Of those, HPV 16 and 18 are associated with an increased risk of developing cervical cancer.
Figure 5-2. The structure of human papilloma virus (HPV). Image adapted from: 306/Shutterstock.com
HPV can be categorised into low & high risk.

● Low-risk HPV is mostly asymptomatic, meaning they usually don’t cause disease & the individual doesn’t have any
symptoms. However, a few low-risk HPV types can cause warts and rarely, cancer.
● High-risk HPV can cause several different types of cancer, with cervical cancer being the most notable. There are ~14
high-risk HPV types – HPV16 & HPV18 are responsible for causing the most HPV-related cancers.
Exercise
In your own words, describe the lesions shown.
Epidemiology of HPV – who gets it?
HPV is a common virus that infects both males & females. An HPV infection can be asymptomatic, meaning an infected
individual may not show any signs or symptoms of the disease but are still able to transmit the virus to others. The virus can
spread easily via direct skin-skin contact and therefore it can be transmitted without sexual intercourse. Up to 90% of the
population will be infected with at least one genital type of HPV sometime in their lives, though the majority of people can clear it
naturally without any treatment or medication. It is only when an individual is unable to clear their HPV infection, are they at risk
of developing cancer.
How does HPV infect and cause disease?
HPV particles spread via direct skin on skin contact. Intact skin is highly resistant to infection and acts as a physical barrier to
infectious agents. Breaks or damages to the skin, however, allow infectious agents such as viruses to enter. These damages to the
skin may occur during vaginal, anal or oral sex. Mucous membranes, which include the inside lining of the mouth, lip, vagina &
anus, are more easily infected by the virus.
Once the virus infects the cell, it produces viral proteins (known as E6 & E7) – these viral proteins interfere with normal cell
division by binding to proteins in the cell which regulate cell division (see Figure 5-3). This results in uncontrolled cell division
which increases cell proliferation, causing wart development.
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Figure 5-3. Viral proteins E6 & E7 bind to proteins which regulate cell division. Binding of the viral protein to these regulator
proteins results in their destruction. The cell therefore loses its ability to regulate its own rate of division.
Tumour Suppressor Proteins

A tumour suppressor protein is encoded for by a tumour suppressor gene. The main function of these proteins is to control
cell replication through repressing genes required for cell division or through apoptosis. Two well-known tumour suppressor
proteins include:
● Retinoblastoma protein (pRb): prevents cell cycle progression from G1 to S phase
● p53: involved in DNA repair, inducing apoptosis & regulating the cell cycle
How does HPV cause cancer?
HPV disrupts the function of tumour suppressor proteins which results in increased cell proliferation. Tumour suppressor proteins
(such as p53) are also involved in DNA repair and apoptosis; therefore, loss of functioning of this protein increases the likelihood
of mutations and their propagation. Viral DNA of HPV may also integrate into the genome of the host cell, which causes further
disruption to the stability of the cell’s DNA.
HPV can cause a variety of different cancers. HPV can cause cervical & vaginal cancer in women & penile cancer in men. HPV
can cause anal & oropharyngeal cancer in both men & women. All these cancer types are caused by persistent HPV infection
(i.e., when the infected individual is unable to clear their infection).
Cervical cancer
Cervical cancer is the growth of abnormal cells within the lining of the cervix. Most cases of cervical cancer are caused by
persistent infection with high-risk HPV types including HPV16 and HPV18.
Epidemiology
Cervical cancer was the 14th most commonly diagnosed cancer among females in 2015 and will likely remain the same this year.
Risk Factors
The biggest risk factor for cervical cancer is persistent infection with high-risk HPV.
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Figure 5-4. The cervix is the lower, narrow part of the uterus which joins the uterus and the vagina.
Cervical screening test
The cervical screening test aims to prevent cervical cancer through early detection and intervention. The screening test looks for
HPV DNA in the cervix and tests for 14 types of HPV. Women aged 25-74 years old are eligible to receive the screening test once
every 5 years. Screening is recommended for individuals who:
● Are between 25-74 years old
● Have a cervix
● Have been sexually active
● Have had the HPV vaccination (why?)
How does the screening test work?
If the test reveals HPV DNA within cervical cells, it is deemed positive. This means further investigation is required, which often
involves a procedure known as a colposcopy test that obtains a biopsy.
Exercise
In your own words, describe the process of the cervical screening test.
Biopsy
A biopsy is a tissue sample used to analyse cells for abnormalities. The following figure illustrates the normal cervical biopsy and
how the abnormalities are categorised:
Figure 3-5. Normal cervical tissue and categorisation of cervical abnormalities. Adapted from:
https://nci-media.cancer.gov/pdq/media/images/752234.jpg
As seen in the diagram, the cells of the cervix are usually highly organised into different layers. The basement membrane lies at
the deepest level. Following a period of persistent HPV infection in the cells near the basement membrane, there may be signs of
productive viral infection. This appearance is known as low-grade squamous intraepithelial lesion (LSIL). LSIL may regress,
persist or progress into high-grade squamous intraepithelial lesion (HSIL). While HSIL may regress, it is considered to be pre-
29
cancerous and thus needs treatments. If left untreated, it may progress to become squamous cell carcinoma (SCC) that invades
beyond the basement membrane.
HPV vaccine: how it works
A vaccine is a substance used to induce an immune response in its recipient. This immune response leads to the development of
‘immune memory’ which allows the recipient’s immune system to ‘remember’ the pathogen (disease-causing agent) contained
within the vaccine. The HPV vaccine, known as Gardasil, consists of virus-like particles (VLPs) which are molecules that
resemble the virus but lack key components that give the virus its ability to cause disease. These VLPs are recognised by the
immune system as if they were the real HPV particle and thus induces an immune response. This leads to the development of
immune memory and consequently, the recipient is protected from future infection by the HPV types included within the vaccine.
Figure 5-6. Once vaccinated, VLP induces the host’s immune system to generate an immune response. Upon encounter with
HPV, memory immune cells act rapidly and with great intensity to eliminate the virus before it can cause any disease.
Gardasil: successes and challenges
Since its implementation, the vaccine has reduced the incidence of high-grade cervical abnormalities by almost 50% in Victorian
girls under 18. There has been a 90% reduction in genital warts in heterosexual men & women under 21. The new Gardasil 9
vaccine is expected to prevent up to 90% of cervical cancers going forward.
Despite its success, Gardasil faces some challenges. There are over 100 types of HPV. The new Gardasil 9 covers 9 types,
meaning vaccinated individuals may still be infected by types not included within the vaccine. Transmission of HPV can also
occur vertically, meaning from mother to child.
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Question 3
Describe the significance of intact skin and its role in providing protection against infective organisms.
Question 4
Describe in your own words the three main ways in which HPV can induce cancer progression in an infected cell.
Question 5
What does the term dysplasia mean?
Question 6
How does Gardasil work? Why is the vaccine given in high school?
Question 7
Why is it important that the Gardasil vaccine is given to boys as well as girls?
Question 8
How can we prevent cervical cancer?
Question 9
Sally is a 27-year-old woman. She has never had a cervical screening test even though she has been sexually active in the past.
Sally’s GP explains that she should have a cervical screening test. Sally is reluctant to have one because she is healthy and does
not think she has any infections. How would you explain to Sally why it is still important for her to have the test?
References
1. Cancer Council Australia Cervical Cancer Screening Guidelines Working Party. National Cervical Screening Program:
Guidelines for the management of screen-detected abnormalities, screening in specific populations and investigation of
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abnormal vaginal bleeding [Internet]. Sydney, NSW: Cancer Council Australia; 2021 [updated 2021 Feb 1; cited 2021
Jun 22]. Available from: https://wiki.cancer.org.au/australia/Guidelines:Cervical_cancer/Screening
2. Cancer Council. Cervical cancer [Internet]. Canberra, ACT: Cancer Council; 2021 [cited 2021 Jun 22]. Available from:
https://www.cancer.org.au/cancer-information/types-of-cancer/cervical-cancer
3. Longworth MS, Laimins LA. Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol
Rev. 2004 Jun;68(2):362-72.
4. Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva, Switzerland: World Health
Organization; 1968. Report No.: Public Health Papers No. 34. Available from:
https://apps.who.int/iris/handle/10665/37650
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Masterclass 6: Cancer Screening and Prevention II
Learning objectives
● To appreciate the screening and prevention techniques used in other common cancer types in Australia
o Breast cancer
o Bowel cancer
o Skin cancer
● Module 8
o Causes and Effects
▪ Investigate the causes and effects of non-infectious diseases in humans, including diseases caused by
environmental exposure and cancer
o Epidemiology
▪ Analyse patterns of non-infectious diseases in populations, including their incidence and prevalence
infectious disease
o Prevention
▪ Use secondary sources to evaluate the effectiveness of current disease-prevention methods and develop
strategies for the prevention of a non-infectious disease
Section 1: Breast cancer
Breast cancer is the most common cancer affecting Australian women – it is estimated that 1 in 8 women will be diagnosed with
breast cancer in Australia by the age of 85. Breast cancer can also affect men, although this is much rarer.
Prevention
Prevention of breast cancer can often start with oneself. This means actively looking for changes in your own breasts. Changes
include:
● A new lump or lumpiness in the breasts, especially if only in one breast
● A change in size & shape of the breast
● Changes to the nipple such as crusting, ulceration, redness or nipple inversion
● Changes to the skin of the breast such as redness, dimpling or puckered skin
● Pain in the breast
Screening
Screening for breast cancer is provided by BreastScreen Australia. The program invites women aged 50-74 without symptoms of
breast cancer to have a free mammogram every 2 years. Mammograms allow for early detection of breast cancers, which usually
results in better patient outcomes. (Note, individuals with higher risk of breast cancer may undergo breast screening from an
earlier age and more frequently.)
A mammogram is an imaging technique that allows for visualisation of structures within the breast. They can reveal abnormal
areas that can prompt further investigations. If the mammogram reveals an abnormality, follow up investigations are typically
performed – this includes a breast ultrasound or MRI. If cancer is suspected, a biopsy is performed to identify and diagnose the
abnormality of the cell.
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Figure 6-1. An illustration showing how mammogram is performed and an example of a mammography. Adapted from:
https://www.cancer.org/cancer/breast-cancer/screening-testsand-early-detection/mammograms/mammogram-basics.html
Pros and cons of breast screening
Section 2: Bowel cancer
Bowel cancer is a cancer of the large intestine, which includes the colon & rectum (see Figure 6-2). It is one of the most common
cancers in Australia, particularly for individuals >50. Approximately 17,000 people are diagnosed with bowel cancer annually.
Early detection allows for 90% of cases to be successfully treated.
Figure 6-2. The anatomy of the large intestine. Adapted from: www.medlineplus.gov
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Screening
Screening for bowel cancer in Australia is provided by the National Bowel Cancer Screening Program (NBCSP). The NBCSP
invites people over age 50-74 without symptoms to participate. Eligible individuals receive a screening kit that allows them to
perform the screen from home. The screen tests for blood in the stool and can also detect blood that is not visible to the naked eye
(known as an occult bleed). If blood is detected, this is a positive result that prompts further investigation. A colonoscopy is
usually the investigation of choice.
A colonoscopy allows a doctor to visualise the large bowel and even take tissue samples (biopsies). The procedure involves
inserting a long flexible tube called a colonoscope into the rectum (see Figure 6-3). The tube has a video camera to allow for
visualisation of the colon.
Figure 6-3. Performing a colonoscopy. During the procedure, a flexible tube with a camera attached is inserted into the rectum to
visualise the large intestine. Adapted from: https://www.mayoclinic.org/tests-procedures/colonoscopy/about/pac-20393569
Abnormalities
Figure 6-4. Left – colonic polyps (small clumps of abnormal cells). Most are harmless; however, some can develop into colon
cancer. Adapted from: https://www.healthline.com/health/colorectal-polyps#risk-factors. Right – Colorectal cancer (abnormal
growth of cells with invasive properties); this means these cells can spread to nearby tissues or other organs in the body. Adapted
from: https://www.sciencephoto.com/media/967247/view/colon-cancer-endoscope-view
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Exercise
In your own words, describe the lesions shown.
Screening outcomes
Initial impact of the National Bowel Cancer Screening Program:

● The increased detection rate of colorectal cancers
● Colorectal cancers detected by the screening tests were diagnosed at earlier stages
Current & future projected impacts:
● Prevent cancer cases
● Reduce the number of deaths from colorectal cancer
Section 3: Skin cancer
Cancer of the skin occurs when skin cells become damaged – typically, this occurs through overexposure to ultraviolet (UV)
radiation from the sun. There are 3 main types of skin cancer:
● Basal cell carcinoma (BCC)
● Squamous cell carcinoma (SCC)
● Melanoma – most dangerous due to its ability to spread throughout the body
Figure 6-5. Left – basal cell carcinoma. Adapted from: https://www.merckmanuals.com/home/skin-disorders/skin-cancers/basal-

cell-carcinoma. Middle - squamous cell carcinoma. Adapted from: https://www.msdmanuals.com/home/skin-disorders/skin-
cancers/squamous-cell-carcinoma. Right – melanoma. Adapted from: https://www.msdmanuals.com/professional/dermatologic-
disorders/cancers-of-the-skin/melanoma.
Epidemiology
Around 2 in 3 Australians will be diagnosed with skin cancer by the time they are 70. Melanoma is the 3rd most common cancer
in Australia. The incidence of skin cancer in Australia is one of the highest in the world.
Screening for and preventing skin cancer
Though no formal screening program exists for skin cancers, many public health campaigns have aimed to raise awareness around
skin cancers. The ABCDE’s of Melanoma is a prominent example that aims to educate people on the differences between a
healthy mole and a malignant melanoma.
36
If you are concerned about a spot or growth of the skin, it is best to consult a professional. Skin cancer clinics exist throughout
Australia and provide thorough examinations of the skin – these are usually run by General Practitioners (GPs) or dermatologists
(skin specialist doctors)
Figure 6-6. Though no formal screening program exists, many public health campaigns have aimed to raise awareness around
skin cancers. The ABCDE’s of melanoma is a prominent example that aims to educate people on the difference between a healthy
mole & a malignant melanoma. Adapted from: https://ocskincancer.com/abcdes-of-melanoma/ and
https://www.healthdirect.gov.au/skin-cancer-prevention.
37
Question 1
What is BreastScreen Australia?
Question 2
What are the pros and cons of performing a breast screen?
Question 3
Jim is a 55-year-old man who recently receives a home testing kit from the National Bowel Cancer Screening Program. Jim
wants to know what the screening test will be used for. How would you explain this to him?
Question 4
You and your friend are going out to play tennis. You remember learning about being SunSmart at the YACI Masterclasses.
How would you explain to your friend why it is important to be SunSmart?
References
1. Australian Government Department of Health. BreastScreen Australia Program [Internet]. Canberra, ACT: Australian
Government Department of Health; 2021 [cited 2021 Jun 21]. Available from: https://www.health.gov.au/initiatives-and-
programs/breastscreen-australia-program
2. Australian Government Department of Health. National Bowel Cancer Screening Program [Internet]. Canberra, ACT:
Australian Government Department of Health; 2021 [cited 2021 Jun 21]. Available from:
https://www.health.gov.au/initiatives-and-programs/national-bowel-cancer-screening-program
3. Cancer Council. Skin cancer [Internet]. Canberra, ACT: Cancer Council; 2021 [cited 2021 Jun 18]. Available from:
https://www.cancer.org.au/cancer-information/types-of-cancer/skin-cancer
38
Masterclass 7: Treatments – Introduction
Learning objectives
● To differentiate the concepts of local and metastatic malignancies

● To appreciate different options for local and systemic therapies
● To understand how the differences between normal cells and cancer can be utilised for targeted cancer therapies

o Epidemiology
infectious disease
Revision
The term cancer does not describe one single disease. It is a group of many diseases arising from various types of tissues due to a
myriad of genetic abnormalities. To expand on how complex cancer is, each cell of a cancerous tumour may be different from
another from the same tumour. Each metastatic tumour may be different from another that is arising from the same primary
tumour (the origin of a metastatic tumour). Each of the cells within a metastatic tumour may also be genetically different from one
another. Additionally, there may be differences between patients who are suffering from the same type of cancer. This variability
of cancer has created a necessity for a generalised framework for understanding cancer in its core. As a result, a seminal review
article written by two cancer researchers, Hanahan and Weinberg, was published to describe the ‘hallmarks of cancer’, or common
characteristics of cancer (refer to Masterclass 1: Basics of Cancer Biology for detailed explanations of the hallmarks).
Figure 7-1. The hallmarks of cancer. Adapted from: Cell 2011 144646-674DOI: (10.1016/j.cell.2011.02.013)
39
Section 1: Treatments
Aims of treatment
There are many things that we need to consider when we choose to treat patients with cancer. The aims of various treatments can
include the following:
● To cure cancer
o Curing cancer is usually the most desirable outcome. As long as this is achievable, our primary aim of treating
cancer is to cure cancer.
● To control symptoms
o Sometimes it may be difficult to completely eradicate the disease, and we may only be able to help alleviate or
control symptoms by treating the patient. For example, if the cancer is causing too much pain, then doctors may
be able to prescribe some pain medications to help patients feel more comfortable.
● To prolong survival
o Regardless of whether cancer is curable or not, prolongation of survival can be an important aspect of cancer
treatment. However, the patients’ quality of life also must be considered. Some patients may prioritise
prolongation of the absolute number of years of life over their quality of life, while others may prioritise the
opposite. Therefore, we need to consider what kind of survival the patient desires.
● To minimise the side effects of treatments
o Treatments for cancer, as we will see, often cause significant side effects to patients. The health professionals
must balance the benefits and side effects of different treatments and attempt to minimise harms to patients.
Local vs Metastatic Cancer
Another factor that we need to consider is whether cancer is confined to one region of the body or has metastasised to other parts
of the body. Cancer can be categorised into the following:
● Local cancer = A malignant cancer that is confined to the organ of its origin
o e.g., A bowel cancer that is only affecting a small part of the large bowel
● Metastatic cancer = A malignant cancer that has spread from its origin to other places in the body usually via blood or
lymph
o e.g., The bowel cancer above may spread to the liver and cause multiple cancerous tumours to grow in the liver.
Figure 7-2. Local vs metastatic malignancies.
A local cancer, depending on its location and size, can be relatively simple in terms of treatment approaches. In many cases, the
removal of the primary tumour may be sufficient to cure cancer. However, even with local cancers, there may be small metastatic
cells (micrometastases) that are floating around in the body that are not able to be detected by imaging devices. Therefore, we
also need to consider the use of other treatment methods to attack those micrometastases.
In a metastatic cancer, on the other hand, detectable metastasis of the primary tumour has occurred. This means that the cancer is
aggressive in its behaviour; therefore, aggressive approaches to attack multiple sites of the cancer may be necessary to prevent the
development of further metastases and slow progression of the disease. This may help with the patient’s symptoms and prolong
40
their life; however, it is most likely that they will not be able to cure the cancer because it has already started to spread and grow
throughout the body.
Local therapies
Some of the treatment options are usually only suitable for localised effect. For a patient with a local malignancy, the treatment of
the affected body region may be sufficient to cure cancer. On the other hand, for a patient with a metastatic disease, it may be
difficult to remove all the cancerous tissues one by one to cure cancer; however, if one of the cancerous sites is producing a local
symptom that is distressing the patient, it may be possible to locally treat that specific site and alleviate the symptom. The
examples of these local therapies are surgery and radiotherapy.
Surgery
Surgery is a procedure performed to physically remove or repair body parts affected by various diseases. In the setting of cancer
treatment, it can have a variety of aims and applications.
● Diagnostic surgery
o For some types of cancers, it may be necessary to remove the diseased tissue and examine it closely before an
accurate diagnosis of cancer can be made. This is called a biopsy. When the biopsy sample is examined under a
microscope, the presence of cancer cells, their characteristics, and the extent of the disease can be determined to
guide health professionals in their management plan for the patients.
● Curative surgery
o In many instances, surgical removal of cancerous tissue can be curative if the cancer is in an early stage (i.e. the
cancer is small and has not metastasised to other parts of the body). During the surgery, surgeons remove the
abnormal tissue along with the surrounding normal tissue to make sure that all abnormal cells that may not be
visible to the eyes are removed as well. They may also remove nearby lymph nodes to which cancer cells may
have metastasised. These tissues are then sent to the laboratory to be examined under the microscope. The
information gained from the laboratory helps health professionals in determining whether any further treatment
will be needed.
● Preventative surgery
o Another application of surgery is to prevent the development of cancer. This can be used for various types of
cancers such as colon cancer and breast cancer. If the overall risk for developing cancer is deemed to be
significant, then the patient may discuss with the doctors about the necessity to undergo preventative surgery.
● Reconstructive surgery
o Surgery can also be used to reconstruct a part of the body that has been removed or affected by cancer
treatments. This image shows a type of breast reconstruction for a patient who has removed one breast.
● Palliative/symptom control surgery
o Sometimes, cancers cannot be fully removed or cured even with other types of treatments. In this case, the
primary goal for patients becomes their quality of life. Therefore, even if the cancers are not able to be
completely removed with surgery, removing at least a part of them that causes symptoms can greatly improve
the patients’ quality of life. An example of this is a surgical removal of a brain lesion even before its exact
diagnosis is known. In some cases, it is not possible to remove the entire mass, but removing at least a part of it
will help reduce the mass-effect (the mass presses on surrounding structures and cause symptoms) and alleviate
neurological symptoms while aiding in diagnosis of the lesion.
Radiotherapy
Radiation is another type of local therapy available for cancer treatment. It uses various forms of high-energy radiation (usually X-
rays) to kill cancer cells by causing damages to their DNA. When the DNA damage is too extensive, the cancer cells no longer
become viable and die. There are several aims of radiotherapy:
● Curative
o On its own or together with other treatment options
● Neoadjuvant
o Radiotherapy before the main treatment (usually surgery) can shrink the tumour or kill micrometastases that are
too small to be detected. This can increase the chance of the main treatment working.
41
● Adjuvant
o Even after the main treatment, some undetectable metastatic cells may survive. Therefore, add-on radiotherapy
after the main treatment can be used to kill residual cells to increase the patient’s overall likelihood of survival.
● Palliative/symptom control
o Palliative radiotherapy may shrink a tumour to relieve symptoms for the patient.
o For example, radiotherapy may be used to shrink bone metastases to reduce pain or prevent spinal cord
compression in the spine.
There are two ways of delivering radiotherapy: from the outside of the body (external), or the inside (internal).
● External radiotherapy
Figure 7-3. Breast radiotherapy using Linear Acclerator Machine (LINAC). Adapted from:
https://www.mayoclinic.org/tests-procedures/radiation-therapy-for-breast-cancer/about/pac-20384940
o Commonly delivered via a machine known as Linear Accelerator Machine (LINAC) that directs a high energy
radiation beam to the body region that contains a tumour. The beam then causes damages to the DNA of cells
that are exposed to radiation.
● Internal radiotherapy
o Internal radiotherapy, on the other hand, delivers radioactive energy from the inside. This method of
radiotherapy is sometimes used for a few types of cancers: thyroid, prostate and liver. As an example, a type of
internal radiotherapy known as brachytherapy involves the insertion of radioactive seeds or implants to the site
of the tumour for a period of time to expose the tissue to radiation.
o Another type of internal radiotherapy is the use of radioactive liquids that are ingested by/injected to patients. A
common example of this is the ingestion of radioactive iodine for thyroid cancers. This is a strategy that
utilises the normal physiology of the thyroid gland, which readily takes up iodine to make hormones.
Systemic therapies
However, the treatment options that we have discussed so far have their limitations in that they are directed toward a specific
region of the body. It would be very difficult to perform surgeries or deliver radiation on every part of the patient’s body,
considering the detrimental effects that they would bring to the patient. Therefore, a way to deliver treatment to multiple cancer
sites is needed. Our bodies contain blood that travels throughout the body to deliver oxygen and important nutrients. We can use
this to our advantage to treat cancers that may have metastasised. Even in local cancers, small metastatic cells that are not
detectable may be present. Therefore, if we can deliver treatments systemically via blood, those treatments can travel throughout
the body and attack cancer cells.
The options for systemic therapies include:

● Chemotherapy
● Hormonal therapy
● Targeted molecular therapy
● Immunotherapy
Chemotherapy
42
Cancer cells will go through the cell cycle to be able to grow and replicate. Chemotherapy involves the use of anti-cancer drugs
that target specific stages of the cell cycle to stop the cell from progressing through the cell cycle. Some drugs bind to the DNA of
cells to inhibit the replication of DNA in the S phase. Other types of drugs may also interfere with the proteins involved in the
mitotic division of cells. Therefore, chemotherapy primarily affects cells that divide rapidly, including cancer cells. However,
other normal cells that divide rapidly (e.g., skin cells, blood cells, inside-lining of the gut) can also be affected and produce side
effects.
Hormonal therapy
Figure 7-4. A generalized diagram of hormone signaling pathway. To interfere with this pathway, drugs that can block the
hormone-producing enzyme or the hormone receptor can be used.
Hormones are signalling molecules that travel in the blood to play an important role in the normal functioning of our bodies (see
Figure 7-4). When they reach cells that have specific receptors for them, they bind to the receptors and activate signalling
pathways inside the cells to instruct cells to perform certain tasks. Some of these hormones are involved in instructing cells to
survive, grow and divide. An example is oestrogen, which stimulates the growth of various cells including those of the breast
tissue. However, if these signals become overactivated, the cells will overgrow and develop into a cancer. In such cases, hormonal
therapy can be used to block the hormone itself or its receptor to slow or stop the growth of cancer cells. In other situations,
hormones may signal cells to be underactive in their functions. Therefore, if we have overactive cancer cells, we can inject certain
hormones to suppress their activities (e.g., glucocorticoids for cancers of the immune cells).
Targeted molecular therapy
Given that cancer cells arise from random genetic mutations, what if we target those specific mutations (i.e., the changes from our
normal cells)? If this is possible, we can target only the cells with those mutations and minimise the collateral damage to the
normal cells without those mutations. Also, we may be able to target the molecular pathways that are directly involved in
development of cancer. Thus came the idea of targeted molecular therapy that uses drugs or substances that target specific
molecules unique to cancer cells. For example, small-molecule drugs that can enter cells easily may be able to block certain
proteins that are in mutated forms that cause cells to grow and divide. However, for targeted molecular therapy to be effective, the
cancer cells must contain the target of those drugs. Also, despite the specificity of targeted molecular therapy for a target, it can
still produce significant side effects in patients.
Immunotherapy
43
Like targeted molecular therapy, certain abnormal proteins produced from mutated genes may be exposed on the surface of the
cancer cells. We can utilise the specificity of the immune system to target those specific proteins. This manipulation and
utilisation of the immune system to target and treat cancer cells is called immunotherapy.
Two of the important components of our immune system are B cells and T cells (refer to Masterclass 1).
● B cells make immune proteins called antibodies, which can bind other foreign proteins on the surface of germs or
cancerous cells
● Some T cells can directly recognise and kill germs and cancerous cells. Other types of T cells can orchestrate the whole
immune system against specific germs or cancerous cells.
A critical feature of these two cell types in their use for immunotherapies is their specificity, or ability to recognise specific
molecules on germs of cancerous cells. Given that there may be specific molecular differences between cancer cells and normal
cells that we can target, these specificities can be utilised to create targeted therapies against certain cancer cells. Some of the
examples of immunotherapy include:
● Monoclonal antibodies
o Different B cells can produce multiple antibodies, each of which has a unique specificity against a target. These
antibodies are termed polyclonal antibodies because they are generated from multiple different clones of B cells.
In the laboratory, we can select one B cell that produces antibodies against a target that cancer cells express.
These antibodies come from many clones of that specific B cell, and are therefore termed monoclonal
antibodies. Monoclonal antibodies can bind to one specific target on cancer cells so that the immune system can
better recognise and destroy them.
● Chimeric antigen receptor (CAR) T cell therapy
o This is novel experimental immunotherapy that is being trialled in Australia for various types of cancers,
particularly those of the blood. In this therapy, T cells are removed from the patient’s blood in the laboratory.
Next, a newly engineered gene that codes for a receptor that can recognise a specific target on cancer cells is
introduced into the T cells. These cells are then returned into the patient’s blood so that they can circulate
around until they recognise the target with their new receptors. Once the recognition occurs, these T cells
replicate themselves and produce various immune reactions against the cancer cells that express the target
protein.
● Checkpoint inhibitors
o While T cells are important in their responses against germs and cancer cells, they have the potential to cause
harm to our normal cells if they become overactivated. Therefore, our body produces ‘checkpoints’ that stop T
cells from being activated and killing healthy cells. However, some cancer cells can overexpress these
checkpoints to stop T cells from recognising and attacking them. Checkpoint inhibitors are drugs that bind to
these checkpoints and enhance the ability of T cells to produce immune reactions against cancer cells.
Consequences of treatments
There may be different consequences following the administration of these treatments:

● Stable disease
o Cancer stays the same size or even grows slightly
● Progression
o Cancer does not respond to the therapies and becomes worse or spreads in the body
● Partial remission
o Some, but not all, signs and symptoms of cancer disappear in response to the treatments
● Complete remission
o All detectable signs and symptoms of cancer disappear in response to the treatments, although cancer may still
be present in the body
o This does not equal cure!
● Recurrence
o Cancer comes back, usually after a period of time during which cancer could not be detected
44
Question 1
What are some of the side effects that we can expect with chemotherapy?
Question 2
What may be some of the side effects of using immunotherapy to enhance the function of the immune system?
Question 3
How might the use of targeted therapies such as targeted molecular therapy or immunotherapy be more advantageous or
disadvantageous over non-targeted therapies such as surgery or chemotherapy?
References
1. Cancer Council. Treatment [Internet]. Canberra, ACT: Cancer Council; 2021 [cited 2021 Apr 11]. Available from:
https://www.cancer.org.au/cancer-information/treatment
2. Hanahan D, Weinberg RA. Hallmarks of cancer. Cell. 2000 Jan;100(1):57-70.
3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar;144(5):646-74.
4. National Cancer Institute. Cancer treatment [Internet]. Bethesda, MD: National Cancer Institute; 2021 [cited 2021 May
28]. Available from: https://www.cancer.gov/about-cancer/treatment
45
Masterclass 8: Treatments – Applications
Learning objectives
● To integrate basic knowledge regarding cancer screening, diagnosis and various treatment options in case studies on
breast cancer and leukaemia
● To appreciate the importance of scientific research in the development of cancer therapies

o Epidemiology
infectious disease
Section 1: Case study 1 – breast cancer
BreastScreen Australia offers women aged 50-74 without symptoms or risks of breast cancer to have a free mammogram every
two years. In patients who are known to have any of those symptoms or risks of breast cancer may be offered to undergo
mammography earlier.
When a suspicious lesion or feature is found on the mammogram, an approach known as ‘the triple test’ is used. This includes:
● Personal medical history (doctors ask about relevant information related to breast cancer symptoms that the patient may
have noticed), and physical examination of the breast
o Breast examination:
▪ Inspection – looking for any visible changes to the breasts (skin, shape, nipples)
▪ Palpation – checking for any palpable changes to the breasts in vertical strips to make sure that all of
the breast tissue is thoroughly examined. Lymph nodes are also checked for any firmness, pain on
palpation, etc.
● Imaging (ultrasound and mammogram used)
● Biopsy
o The method of taking a breast tissue biopsy is called a core needle biopsy (see Figure 8-1). This type of biopsy
allows doctors to take a small section of the tissue without destroying its architecture/shape. The biopsy is then
sent to the laboratory, and pathologists can use certain dyes to visualise the tissue under the microscope. Based
on these appearances, the pathologists can give a preliminary diagnosis and grade the tissue according to how
abnormal these tissues appear.
46
Figure 8-1. Core needle biopsy. This biopsy method is used to obtain a small sample from various tissues such as breast tissue.
Adapted from: https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/breast-biopsy/core-needle-biopsy-
of-the-breast.html
There are many types of procedures available for breast cancer patients, and one of the common procedures is called breast-
conserving surgery or lumpectomy. During this surgery, nearby lymph nodes can also be removed to look for any lymph node
spread. Breast-conserving surgery allows the conservation of normal breast tissues. However, for breast cancers that have spread
and metastasised, it may not be sufficient, and the patients may need to consider other types of procedures.
Staging & Typing of Cancer
After the surgery, removed breast tissues and lymph nodes are examined again under the microscope to determine further
management plan for the patient.
● Staging = determining how advanced the cancer is/how far the cancer has spread
o TNM staging method commonly used
▪ T (Tumour size)
● How large is the tumour?
▪ N (Lymph node involvement)
● Are there any lymph nodes that have been invaded by the cancer cells?
▪ M (Metastasis)
● Has the cancer spread to a distant body site?
● Typing
o Breast cancer cells may or may not express certain proteins (e.g., oestrogen receptors - OR, progesterone
receptors - PR, HER2 receptors) on their surfaces
o The presence/absence of these can help doctors determine the patient’s likely outcome after the surgery. This
also helps guide further treatments
▪ If we know what proteins the cancer cells express, we can target them to destroy any residual cancer
cells that may be present
Depending on the stage of the cancer, we may need to consider the possibility of residual cancer cells being present in the body. If
this is likely, patients may receive adjuvant radiotherapy of the affected breast. In addition, we may also prescribe patients with
other adjuvant therapies depending on the type of breast cancer cells (i.e., presence/absence of OR, PR, HER2). For example, in
ER+ breast cancers, oestrogen binds onto the oestrogen receptor to promote growth and division of the breast cancer cells.
However, drugs such as tamoxifen can interfere with this oestrogen signalling pathway and inhibit their growth (see Figure 8-2).
Figure 8-2. The mechanism of action of tamoxifen for the use of breast cancer treatment. Tamoxifen binds to the oestrogen
receptor and blocks the binding of oestrogen to inhibit cell growth.
As another example, HER2 molecules are sometimes also overexpressed on breast cancer cells to promote their growth. These
molecules can be blocked using immunotherapeutic antibodies called trastuzumab (see Figure 8-3).
47
Figure 8-3. The mechanism of action of trastuzumab. The anti-HER2 antibody, trastuzumab, blocks the action of HER2 to inhibit
the growth of cancerous cells.
The decision of which treatment options to be used for patients is dependent on many factors such as the cancer’s stage and type.
Different patients have different breast cancers; therefore, treatments have to be tailored to individual patients according to the
best available evidence. This notion is termed ‘personalised medicine’ (also known as precision or stratified medicine).
Question 1
What are the factors that doctors should consider when deciding which treatments to be employed for patients with breast
cancer?
Section 2: Case study 2 – leukaemia
All blood cell types arise from a single origin: haematopoietic stem cells that reside mainly in the bone marrow. As these cells
develop, they go through certain developmental pathways to end up as different types of blood cells.
48
Figure 8-4. The developmental pathways of blood cells from the haematopoietic stem cell (multipotent stem cell). Adapted from:
https://app.pulsenotes.com/medicine/haematology/notes/haematopoiesis
● Myeloid lineage:
o Red blood cells that deliver oxygen to tissues
o Platelets that help the blood clot
o Various immune cells involved in the first-line immune defence
● Lymphoid lineage (the following are called lymphocytes):
o Natural killer cells that are part of the first-line immune defence
o B lymphocytes that produce antibodies
o T lymphocytes that either orchestrate the whole immune system or directly kill abnormal cells
Leukaemia is the cancer of white blood cells that arise in the bone marrow. The cancerous white blood cells can originate from
either of the two lineages above. As these white blood cells begin to grow and divide, their normal functions of fighting against
pathogens such as infectious organisms become impaired. In addition, they interfere with the normal blood cell-producing
function of the bone marrow.
49
Extension material
Blood smear
The pathology laboratory can take a sample of blood from the patients and count the different types of blood cells. Also, the
blood sample can be smeared onto a thin glass to examine it under the microscope. The main component of the normal blood
smear is the red blood cells with a few white blood cells and some platelets. However, in leukaemic patients, an increased
number of white blood cells may be visible. In severe cases, the visible number of red blood cells and platelets may also be
decreased. However, it is difficult to distinguish different types of white blood cells, particularly lymphocytes, under the
microscope. Therefore, a special technique called flow cytometry is used to sort them out.
Flow cytometry
Figure 8-5. Flow cytometry as a tool to differentiate different types of cells. Adapted from:
https://www.abcam.com/protocols/introduction-to-flow-cytometry
Flow cytometry involves staining of cells using monoclonal antibodies (tagged with fluorescent labels) that can attach to
different surface molecules that are specific to each type of cell. The flow cytometry machine contains a narrow passage
through which a single column of cells can pass through. As the cells pass through the column, laser light is directed toward
the cells. Depending on how much of the laser light passes through each cell and how much of it is scattered, the machine can
plot each individual cell onto a graph. In the meantime, the fluorescence from the labels attached to the antibodies is also
detected by the machine to tell which type of cells they are.
Bone marrow biopsy
Another investigation that can be performed for a patient showing an abnormality in the bone marrow function (i.e., production
of blood cells), it is reasonable to take a bone marrow biopsy to make sure that there is no other cause of the abnormality and
confirm the presence of progressive leukaemia in our case. The biopsy is then examined under the microscope. Normal bone
marrow tissue should contain a variety of different blood cell types; however, in leukaemic patients, there may be an increased
number of leukaemic cells along with a decreased amount of other types of blood cells.
50
Genetic testing
Genetic testing of the cancer cells may also be warranted in addition to the bone marrow biopsy. This allows us to determine
the patient’s risk of progressing further because certain genetic mutations or abnormalities may be associated with poorer
outcomes. Also, some genetic mutations may be able to be targeted with specific molecular or immunotherapies for treatment.
Treatments
So far throughout the masterclasses, many of the cancer types that we have talked about are of solid organs. However, blood is not
solid, and it circulates throughout the body. Therefore, by definition, blood cancers are systemic. This means that we have to
employ systemic treatments to treat our patient. There are many types of systemic therapies are available for patients with blood
cancers, and the decision of which to use for a patient is guided by evidence gained from various clinical trials of different drugs.
For example, B cell chronic lymphocytic leukaemia may be treated with Obinutuzumab, an antibody immunotherapy that targets
CD20 protein expressed on the surface of B cells. Then, other normal immune cells and substances may recognise Obinutuzumab
bound to CD20 and start attacking the cells expressing CD20 (see Figure 8-6).
Figure 8-6. The mechanism of action of Obinutuzumab, an anti-CD20 monoclonal antibody. Obinutuzumab can ‘flag’ B cells by
binding onto CD20 molecules and recruiting immune cells.
Another drug that has been approved to be used for chronic lymphocytic leukaemia along with Obinutuzumab is a targeted
molecular therapy called Venetoclax (see Figure 8-7). This is a drug that has been co-developed and trialled in Australia based on
important research conducted at the Walter and Eliza Hall Institute of Medical Research (WEHI). At WEHI, it was discovered
that a protein known as BCL-2 promotes cell survival. It helps cancer cells survive by blocking apoptosis, a programmed cell
suicide mechanism. If this protein can be targeted with a drug, then its inhibition of apoptosis would be removed, and cancer cells
would die. This is what Venetoclax was shown to achieve. Venetoclax can enter cancer cells that overexpress BCL-2 and induce
their apoptosis.
Figure 8-7. Venetoclax can block the action of a protein that inhibits cellular apoptosis, known as BCL-2. This induces apoptosis
to kill cancer cells.
51
Question 2
What side effects might arise if Obinutuzumab was used to target all B cells that express CD20?
Question 3
Discuss how blood cancers are different from solid cancers (e.g., breast cancer, colon cancer, liver cancer), and how their
treatment options may vary.
Conclusion
To conclude, these case studies highlight the variability that cancers and their treatments can have. Health professionals can use a
variety of investigation methods to accurately characterise and diagnose cancers. They also highlight the importance of scientific
research in the development of an array of treatment options for cancer. Basic understanding of how normal and cancerous cells
behave can give us clues about how cancer and other diseases can be treated. And most importantly, patients must come first in
many considerations that have to be made in the decisions regarding cancer treatment. The term personalised medicine does not
only mean selecting certain treatments for specific types of cancer. It also implies that the patients’ desires, emotions, and lifestyle
factors also must be taken into account to achieve the most favourable and reasonable outcome for patients. All cancer treatments
can have both benefits and side effects; therefore, health professionals and patients should engage in discussions together to
optimise treatments.
References
1. Australian Government Cancer Australia. Triple test [Internet]. Canberra, ACT: Australian Government Cancer
Australia; 2020 [updated 2020 Oct 20; cited 2021 Apr 11]. Available from: https://www.canceraustralia.gov.au/affected-
cancer/cancer-types/breast-cancer/triple-test
2. Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of
trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant
(HERA) trial. Lancet. 2017 Mar;389(10075):1195-1205.
3. Fischer K, Al-Sawaf O, Bahlo J, Fink A, Tandon M, Dixon M, et al. Venetoclax and Obinutuzumab in patients with CLL
and coexisting conditions. N Engl J Med. 2019 Jun;380(23):2225-36.
4. Kenneth M, Casey W. Janeway’s immunobiology. 9 th ed. New York: Garland Science; 2016.
52

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2023

● Online Syllabus Team:

o Masterclass 1 – Basics of Cancer Biology: Isabella Papalia, Nakjun Sung

● To understand different components of a mammalian cell and their functions

In the Biology Syllabus

Section 1: Introduction to cells

Cells and cancer

Figure 1-2. A cell and its organelles. Adapted from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/organelle

In the nucleus: DNA

The central dogma

Section 2: The life of a cell

The cell cycle

Figure 1-5. The cell cycle.

G2: Interphase: Gap 2

Errors in the DNA and their consequences

1. Successful repair, and the cell returns to the cell cycle

Section 3: Basics of immunology

● 1st line defence

● To understand the terms ‘cancer and ‘tumour’

In the Biology Syllabus

● Module 6: Genetic Change

Section 1: Basics of cancer biology

(Note: some benign tumours can become malignant.)

1. Sustaining proliferative signalling

Section 2: Models of cancer progression

Linear progression model

● To gain knowledge of the types of genetic mutations

In the Biology Syllabus

1. Point mutation (see Figure 3-1)

Figure 3-1. Types of point mutations. Adapted from: https://en.wikipedia.org/wiki/Point_mutation#/media/File:Point_mutations-

PET THE DOG FAN…

...DOG AND PAT...

PET THE DOG END...

PAT THE DOG...

Tumour suppressor genes (TSGs)

Figure 3-3. The two-hit model of tumour suppressor genes.

Example: Ras and Myc as oncogenes

Case Study: Genes involved in Breast Cancer

What is the HER2 gene?

What is the BRCA genes?

Why does understanding the genes involved in breast cancer matter?

● To distinguish between ‘cause’ and ‘risk factor’

In the Biology Syllabus

● Module 8: Non-Infectious Diseases and Disorders

Section 1: Lifestyle, environment and cancer

How is a risk factor different from a cause?

Metabolic risk factors

What kinds of radiation are there?

Why is asbestos harmful?

● To understand why we screen for cancers

In the Biology Syllabus

● Module 7: Infectious Diseases

Section 1: Principles of screening and prevention

Cancer screening – what is it and why do we do it?

World Health Organisation (WHO) – Features of a good screening test

Figure 5-1. Sensitivity and specificity

Lifestyle changes include:

Human Papilloma Virus

HPV can be categorised into low & high risk.

In your own words, describe the lesions shown.

Epidemiology of HPV – who gets it?

How does HPV infect and cause disease?

Tumour Suppressor Proteins