Seren Award

Why have we still not

managed to cure cancer?
Angela Andrianopoulou
Cancer Institute, Division of Medicine, UCL
A note…

• Cancer is a disease that unfortunately affects many

people and can be a sensitive topic
• You will NOT be required to share any personal or private
experiences
• If uncomfortable or any concerns, let me know
 Session 1
Understanding cancer
Learning objectives

• Explain how errors in DNA replication and mitosis can lead

to cancer
• Outline the role of mutations in the development of
cancer
• Use pedigrees/family trees to understand someone’s risk of
developing cancer with relevant family history
What is cancer? What do you know
about it?
• Go to www.menti.com and use the code 1039 1312
• Write down some words or phrases that come to mind
 The Cell Cycle

Gap 0 (G0): Resting Stage

Gap 1 (G1): Growth

Synthesis (S): DNA Replication

Gap 2 (G2): Growth

Mitosis (M): Nuclear Division and

Cytokinesis

https://www.cellsalive.com/cell_cycle_js.htm
Control

• Checkpoints in G1 and G2:

o Look for DNA damage and try to repair it.
o Damage that is so severe that it cannot be repaired → self-
destruction by apoptosis.
• Mitosis checkpoint: detects failure of spindle fibers to
attach to kinetochores and will arrest cell in metaphase
until corrected
Mutations

• All checkpoints require the function of a complex of proteins. Mutations in

the genes encoding some of these proteins have been associated with
cancer.
• Checkpoint failures due to gene mutations allow the cell to continue
dividing despite damage to its integrity.
Mutations

• When you bake a cake, you follow a recipe in a cookbook.

DNA is like your body’s cookbook; DNA is read, resulting in
proteins.
• However, sometimes there can be mistakes in the cookbook
• Some substitutions can be made and have no effect, others
will ruin the recipe; you can add to much or too little
• Two types of mutations that can lead to uncontrolled cell
division and cancer: tumour suppressor gene mutations and
proto-oncogene mutations
Mutations: Tumour Suppressor Genes

• When a tumour suppressor gene is

mutated, there is loss of function → cell
cycle checkpoint failure and
uncontrolled division of abnormal cells.
• Like the brakes of a car: brakes don’t
work → car out of control
• Recessive: both alleles need to be
mutated to cause cancer
Mutations: Proto-Oncogenes

• When a proto-oncogene is mutated (now

called oncogene), there is gain of function
→ cell cycle checkpoint failure and
uncontrolled division of abnormal cells
• Like the gas pedal of a car: if the gas pedal
gets stuck in the “on” position → car keeps
moving whether the pedal is pushed or not

• Dominant: only one allele needs to be

mutated to cause cancer.
Quiz

• Go to www.menti.com and use the code 1039 1312

Family history

• Why do cancer cells grow out of control in the first place?

• Let’s take a look at the BRCA gene…
• BRCA1 and BRCA2 (Breast Cancer gene 1 and 2):
• Associated with early-onset breast cancer, ovarian cancer, and
fallopian tube cancer
• Also linked to male breast cancer, pancreatic cancer,
melanoma, and early-onset prostate cancer
• TUMOUR SUPPRESSOR GENES (but dominant)
• Normal role: repair of DNA double strand breaks
Family trees/pedigrees
Quiz

• How many generations are shown in the pedigree?

• What does the pedigree reveal about the family’s history
of breast cancer?
• If someone has a mutated BRCA gene, does that mean
they have or will have breast cancer? Why?

Go to www.menti.com and use code 1039 1312

Questions?