CANCER

Introduction :
Cancer is defined as an uncontrolled proliferation of
cells without any differentiation. Cancer is a group of more than
200 different diseases , where malignant growth or
enlargement of tissue occurs due to unlimited and uncontrolled
mitotic cell division of certain cells and invades surrounding
tissues , forming tumours . Simply cancer can be defined as
mitosis run amok.The progression from normal cells to cells that can form a
detectable mass to outright cancer involves multiple steps known as malignant progression.

Tumors :
What is a tumor ?
A tumor, also known as a neoplasm, is an abnormal mass of tissue which may be
solid or fluid-filled.
There are many different types of tumors and a variety of names for them - their
names usually reflect their shape and the kind of tissue they appear in. Put simply, a
tumor is a kind of lump or swelling, it does not necessarily pose a health threat.

Types of tumors :
1) Benign tumors
A benign tumor (benign neoplasm) cannot metastasize - it cannot spread.
Examples include uterine fibroids , adenomas , moles. "Benign" means it is nonprogressive, it remains as it is.
Most benign tumors are not harmful to human health. Even though they are not
cancerous, some may press against nerves or blood vessels and cause pain or other
negative effects. Benign tumors of endocrine tissues may result in the excessive
production of some hormones.

2) Premalignant tumors
A premalignant or precancerous tumor is one that is not yet malignant, but is
about to become so.
Examples : Actinic keratosis - also known as senile keratosis, Dysplasia of the
cervix , Metaplasia of the lung , Leukoplakia.

Malignant tumors
Malignant tumors are cancerous tumors, they tend to become progressively
worse, and can potentially result in death. Unlike benign tumors, malignant ones
grow fast, they are ambitious, they seek out new territory, and they spread
(metastasize). Malignant tumors divide and spread rapidly, colonizing new areas through
the blood stream.The abnormal cells that form a malignant tumor multiply at a faster
rate.

Characteristics of cancerous cells :

The Hallmarks of Cancer is a seminal peer-reviewed article published in the journal Cell in
January 2000 by the cancer researchers Douglas Hanahan and Robert Weinberg which gave out
the six traits or hallmarks a cancerous cell should posses.

1) Self-sufficiency in growth signal :

Cancer cells do not need stimulation from external signals
Typically, cells of the body require hormones and other molecules that act as signals for
them to grow and divide. Cancer cells, however, have the ability to grow without these
external signals. There are multiple ways in which cancer cells can do this: by producing
these signals themselves, known as autocrine signalling( by permanently activating the
signalling pathways that respond to these signals , or by destroying 'off switches' that
prevents excessive growth from these signals (negative feedback)) . In these cells, the
processes are deregulated because the proteins that control them are altered, leading to
increased growth and cell division within the tumor.

2) Insensitivity to anti-growth signals :

Cancer cells are generally resistant to growth-preventing signals from their neighbours.
To tightly control cell division, cells have processes within them that prevent cell growth
and division. These processes are orchestrated by proteins known as tumor supressor
genes. These genes take information from the cell to ensure that it is ready to divide, and
will halt division if not . In cancer, these tumour suppressor proteins are altered so that
they don't effectively prevent cell division, even when the cell has severe abnormalities.
Another way cells prevent over-division is that normal cells will also stop dividing when
the cells fill up the space they are in and touch other cells; known as contact inhibition.
Cancer cells do not have contact inhibition, and so will continue to grow and divide,
regardless of their surroundings.[

3) Evasion of apoptosis :
Apoptosis is a form of programmed cell death (cell suicide), the mechanism by which
cells are programmed to die in the event they become damaged.
Cells have the ability to 'self-destruct' i.e. apoptosis. This is required for organisms to
grow and develop properly, for maintaining tissues of the body, and is also initiated when
a cell is damaged or infected. Cancer cells, however, lose this abilityof apoptosis ; even
though cells may become grossly abnormal, they do not apoptose. The cancer cells may
do this by altering the mechanisms that detect the damage or abnormalities. This means
that proper signalling cannot occur, thus apoptosis cannot activate. They may also have
defects in the downstream signalling itself, or the proteins involved in apoptosis, each of
which will also prevent proper apoptosis.

4) Limitless replicative potential :

Non-cancer cells die after a certain number of divisions(Hayflicks limit : about 6070
doubling). Cancer cells escape this limit and are apparently capable of indefinite growth
and division . But those immortal cells have damaged chromosomes, which can become
cancerous.
Cells of the body don't normally have the ability to divide indefinitely. They have a limited
number of divisions before the cells become unable to divide(senescence) . The cause of
these barriers is primarily due to the DNA at the end of chromosomes, known
as telomeres. Telomeric DNA shortens with every cell division, until it becomes so short it
activates senescence, so the cell stops dividing. Cancer cells bypass this barrier by
manipulating enzymes that increase the length of telomeres. Thus, they can divide
indefinitely, without initiating senescence.

5) Induction and sustainment of angiogenesis :

Angiogenesis is the process by which new blood vessels are formed. Cancer cells
appear to be able to kickstart this process, ensuring that such cells receive a continual
supply of oxygen and other nutrients.
An expanding tumour requires new blood vessels to deliver adequate oxygen to the
cancer cells, and thus exploits these normal physiological processes for its benefit. To do
this, the cancer cells acquire the ability to orchestrate production of new vasculature by
activating the 'angiogenic switch'. In doing so, they control non-cancerous cells that are
present in the tumor that can form blood vessels by reducing the production of factors
that inhibit blood vessel production, and increasing the production of factors that promote
blood vessel formation.

6) Activation of metastasis and invasion of tissues :

Cancer cells can break away from their site or organ of origin to invade surrounding
tissue and spread (metastasize) to distant body parts.
One of the most well known properties of cancer cells is their ability to invade
neighboring tissues. It is what dictates whether the tumor is benign or malignant, and is
the reason for their dissemination around the body. The cancer cells have to undergo a
multitude of changes in order for them to acquire the ability to metastasize. It is a
multistep process that starts with local invasion of the cells into the surrounding tissues.
They then have to invade blood vessels, survive in the harsh environment of the
circulatory system, exit this system and then start dividing in the new tissue.

In his 2010 NCRI conference talk, Hanahan proposed four new hallmarks. These were later
codified in an updated review article entitled "Hallmarks of cancer: the next generation".
Deregulated metabolism
Most cancer cells use abnormal metabolic pathways to generate energy, a fact
appreciated since the early twentieth century with the postulation of the Warburg
hypothesis,but only now gaining renewed research interest.
Evading the immune system

Cancer cells appear to be invisible to the bodys immune system

Unstable DNA
Cancer cells generally have severe chromosomal abnormalities, which worsen as the
disease progresses.
Inflammation
Recent discoveries have highlighted the role of local chronic inflammation in inducing
many types of cancer.

Theories related to causes of cancer :

1) Mutation theory:
A major impediment to progress is the deep entrenchment of a 50 yearold paradigm, the so-called somatic mutation theory. It goes like this. A
somatic cell serially accumulates genetic damage, eventually reaching a
point at which it decouples from the organism's regulatory systems and
embarks on its own agenda.
2) Selective gene activation theory :
This theory explains that certain genes that are not normally expressed , suddenly
become active and their product causes cancer , as in the case of proto-oncogenes .
A proto-oncogene is a normal gene ,which encode for proteins that help to regulate cell
growth and differentiation . Proto-oncogenes are often involved in signal
transduction and execution of mitogenic signals, usually through their protein products.
These could become an oncogene due to mutations or increased expression. The
resultant protein encoded by an oncogene is termedoncoprotein. Upon activation, a
proto-oncogene becomes a tumor-inducing agent, an oncogene. Examples of protooncogenes include RAS, WNT, MYC, ERK, and TRK.
Ways of activation of proto-oncogenes:
The proto-oncogene can become an oncogene by a relatively small modification of its original
function. There are three basic methods of activation:
1. A mutation within a proto-oncogene, or within a regulatory region , can cause a change in
the protein structure
2. An increase in the amount of a certain protein (protein concentration), caused by

an increase of protein expression (through misregulation)

an increase of protein (mRNA) stability, prolonging its existence and thus its
activity in the cell

gene duplication , resulting in an increased amount of protein in the cell

3. A chromosomal translocation

Types of cancer :
From a histological standpoint there are hundreds of different cancers, which are grouped
into six major categories:

Carcinoma

Sarcoma

Myeloma

Leukemia

Lymphoma

Mixed Types

Carcinoma
Carcinoma refers to a malignant neoplasm of epithelial origin or cancer of the internal or
external lining of the body. Carcinomas, malignancies of epithelial tissue, account for 80 to
90 percent of all cancer cases.
Carcinomas are divided into two major subtypes: adenocarcinoma, which develops in an
organ or gland, and squamous cell carcinoma, which originates in the squamous epithelium.
Adenocarcinomas generally occur in mucus membranes and are first seen as a thickened
plaque-like white mucosa. They often spread easily through the soft tissue where they occur.
Squamous cell carcinomas occur in many areas of the body.
Most carcinomas affect organs or glands capable of secretion, such as the breasts, which
produce milk, or the lungs, which secrete mucus, or colon or prostate or bladder.

Sarcoma
Sarcoma refers to cancer that originates in supportive and connective tissues such as
bones, tendons, cartilage, muscle, and fat. Generally occurring in young adults, the most
common sarcoma often develops as a painful mass on the bone. Sarcoma tumors usually
resemble the tissue in which they grow.
Examples of sarcomas are:

Osteosarcoma or osteogenic sarcoma (bone)

Chondrosarcoma (cartilage)

Leiomyosarcoma (smooth muscle)

Rhabdomyosarcoma (skeletal muscle)

Mesothelial sarcoma or mesothelioma (membranous lining of body cavities)

Fibrosarcoma (fibrous tissue)

Angiosarcoma or hemangioendothelioma (blood vessels)

Liposarcoma (adipose tissue)

Glioma or astrocytoma (neurogenic connective tissue found in the brain)

Myxosarcoma (primitive embryonic connective tissue)

Myeloma
Myeloma is cancer that originates in the plasma cells of bone marrow. The plasma cells
produce some of the proteins found in blood.

Leukemia

Leukemias ("liquid cancers" or "blood cancers") are cancers of the bone marrow. The
disease is often associated with the overproduction of immature white blood cells. These
immature white blood cells do not perform as well as they should, therefore the patient is
often prone to infection. Leukemia also affects red blood cells and can cause poor blood
clotting and fatigue due to anemia.
Examples of leukemia include:

Myelogenous or granulocytic leukemia (malignancy of the myeloid and granulocytic

white blood cell series)
Lymphatic, lymphocytic, or lymphoblastic leukemia (malignancy of the lymphoid and
lymphocytic blood cell series)
Polycythemia vera or erythremia (malignancy of various blood cell products, but with
red cells predominating)

Lymphoma
Lymphomas develop in the glands or nodes of the lymphatic system, a network of vessels,
nodes, and organs (specifically the spleen, tonsils, and thymus) that purify bodily fluids and
produce infection-fighting white blood cells, or lymphocytes. Unlike the leukemias which are
sometimes called "liquid cancers," lymphomas are "solid cancers." Lymphomas may also
occur in specific organs such as the stomach, breast or brain. These lymphomas are
referred to as extranodal lymphomas. The lymphomas are subclassified into two
categories: Hodgkin lymphoma and Non-Hodgkin lymphoma. The presence of ReedSternberg cells in Hodgkin lymphoma diagnostically distinguishes Hodgkin lymphoma from
Non-Hodgkin lymphoma.

Carcinogens :
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in
causing cancer. This may be due to the ability to damage the genome or to the disruption of
cellular metabolic processes. Several radioactive substances are considered carcinogens, but
their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha
particles, which they emit. Common examples of non-radioactive carcinogens are
inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates
carcinogenicity with synthetic chemicals, it is equally likely to arise in both natural and synthetic
substances.[1]Carcinogens are not necessarily immediately toxic, thus their effect can be
insidious.

Types :

1)

Physical carcinogens : They include ionising X-rays, -rays and nonionising UV radiations.

2)

Chemical carcinogens : Includes caffeine , nicotine , pesticides ,

combustion products of coal & petrol.

3)

Biological carcinogens : Includes viruses like HPV causing cancer ,

Epstein-barr virus causing Burkitts lymphoma.

Cancer detection and diagnosis :

Successful treatment of cancer requires early detection of the disease.
Histopathological studies of the tissue and blood , bone marrow tests for
increased cell counts and biopsy are methods for detecting cancer. Besides
these radiography , CT (Computed Tomography) scan , MRI (Magnetic
Resonance Imaging) scan are used to detect cancer of internal organ.

General Treatments to cancer :

1) Radiation Therapy :
Exposure of cancerous parts to X-rays, which destroy rapidly
growing cells. Radioisotopes like Radon(Rn-220), Cobalt(Co-60),
Iodine(I-131) are used in it.
2) Chemotherapy :
Involves the administration of certain anticancer drugs, which
check cell division. Patients are given substances called biological
response modifiers (e.g., interferon) which activate immune
system and destroy tumor. These drugs have side effects like hair
loss, anaemia, etc.
3) Immunotherapy :
It involves natural anticancer immunological defence mechanism.
Monoclonal antibodies are used in it, e.g., radioimmunotherapy.

Case Study 1 : Leukaemia

Case Study 2 : Lymphoma

Case Study 3 : Lung Cancer