CANCER BIOLOGY

In multicellular organisms, cell division is a normal process. Cells divide for

growth, for the development of organs, for healing of wounds and also for the
replacement of older and damaged cells. Cell division is a very complex process
which is controlled by a regulatory mechanism at both molecular and cellular level.

Cancer can be defined as uncontrolled proliferation of cells without any

differentiation. The uncontrolled cell growth produces a mass of cells which are
called tumours or neoplasm. The process of cell change in which a normal cell loses
its ability to control its rate of division and thus becomes a tumour cell is called cell
transformation.

Tumours are of 2 types

A benign tumor: It remains confined to its original location. They do not invade the
surrounding normal tissues. They do not spread to distant body sites. The most
common example of tumour is the skin wart. A benign tumour consists of closely
resembles normal cells and may function like normal cells. Generally benign tumours
are harmless and can usually be removed surgically. However, these tumours may
sometimes become quite harmful if they are located in organs like brain and liver.

A malignant tumour: It does not remain confined to its original location. They are
capable of both invading surrounding normal tissue and spreading throughout the
body via the circulatory or lymphatic systems and form secondary tumour called
metastasis. Malignant tumours become life-threatening if, they spread throughout the
body. Only malignant tumours are properly designated as cancers. The cells of
malignant tumour are derived from single cell, thus they are monoclonal in character.
Malignant tumours are generally classified into four main types on the basis of cell
type from which they arise.

(i) Carcinomas: It includes approximately 90% of human cancer. This type is

principally derived from epithelial cells of ectoderm and endoderm. Cervical, breast,
skin and brain carcinomas are developed from malignant tumour.

(ii) Sarcomas: Sarcomas are solid tumours of connective tissues such as

muscle, bone, cartilage and fibrous tissue. This type of malignant tumours is rare in
human (about 2% of human cancer).

(iii) Lymphomas: It is a type of malignancy in which there is excessive

production of lymphocytes by the lymph nodes and spleen. It accounts for
approximately 8% of human cancers.
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 (iv) Leukemia’s: This type of malignancy arises from the blood forming cell.
Leukemia’s are commonly known as blood cancer. Leukemia’s are neoplastic growth
(uncontrolled cell growth at the cost of remaining cells) of leucocytes or WBC.

Characteristic features of Cancer Cells:

(i) Immortalization: Normal cell cultures do not survive indefinitely. For

example, human cell cultures die after about 50 generations. On the other hand,
transformed cell cultures can go on indefinitely.

(ii) Contact Inhibition is absent: Normal cells growing in tissue culture tend
to make cell contacts by forming adhesive junctions to neighboring cells. When
normal cells have become completely surrounded by other cells, their mobility stops
and they form a monolayer. At the same time there is inhibition of growth occurs in
the point of adhesive junctions. Whereas the cancer cells do not show any adhesive
junctions, it enables the cells to dissociate from neighbouring cells and show loss of
contact inhibition and show continuous growth.

(iv) Invasiveness: It is the ability to invade other tissues. Malignant cells

gener-ally secrete proteases that digest extracellular matrix components, allowing the
cancer cells to invade adjacent normal tissues. Cancer cells also secrete growth
factors that promote the formation of new blood vessels. This is known as
angiogenesis. Angiogenesis is necessary to support the growth of tumour beyond the
size of about a million cells. Actually the growth factor secreted by the tumour cells
stimulates the endothelial cells present in the wall of capillaries. As a result, new
outgrowth of the capillaries is formed into the tumour.

(v) Absence of Differentiation: Normal cells are fully differentiated. In most

fully differentiated cells, cell division ceases. All of the different types of blood cells
develop from a common pluripotent stem cell in the bone marrow. Some of the
descended cells develop erythrocytes but others differentiate to form lymphocytes,
granulocytes and macrophages. In case of cancer cells, normal differentiation
program is blocked at the early stages of differentiation. ie, the blood cells become
blocked at early stage of maturation at which they retain their capacity for
proliferation and continue to divide, which leads to leukemia.

(vi) Density dependent inhibition is absent: In normal cells, cells grow with
growth factor but after a particular stage division stops. Whereas tumour cells
synthesis growth factor and shows continuous division ie, its receptor for growth
factor is mutated. So signal may alter, leads to uncontrolled growth.

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 (vii) Absence of apoptosis: In normal cells, any alterations in division lead to
apoptosis. In cancer cells, there is no apoptosis.

 APOPTOSIS: For every cell, there is a fixed span of life, i.e., time to live and
time to die. This cell death is a very orderly process and so it is called
Programmed Cell Death or PCD or Apoptosis. Apoptosis is a mechanism of
programmed cell death or cell suicide which is essential for the survival of the
organism. It also protects the organism by removing damaged cells which may
be due to viral infection or due to exposure to radiations. It also inhibits the
tumour development and so any defect in the control of apoptosis may lead to
cancer.

Cell death occurs mainly by 2 methods

1. Death by injury that is through mechanical damage or due to toxic chemicals.

2. By Apoptosis, i.e., through programmed cell death.

Morphological changes occurs during apoptosis:

 Shrinkage of the cell.

 Shrinkage of the nucleus
 Loss of adhesion to the neighboring cells
 Formation of membrane blebs (externalization of inner leaflet of membrane)
 Decay of mRNA
 Condensation and fragmentation of the chromatin (DNA)
 Formation of small fragmented chromatin in membrane bounded structures
called apoptotic bodies
 Rapid engulfment of the apoptotic cell debris by the process of phagocytosis

Based on the source of stimuli, there are two types of apoptosis signaling
pathways operate in the cells. They are

(1) Intrinsic pathway of apoptosis (stimuli are internal) - Mitochondria Mediated

Programmed Cell Death Pathway

(2) Extrinsic pathway of apoptosis (stimuli are external) - Receptor Mediated

Programmed Cell Death Pathway

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 Severe DNA damage activate Bax protein (promotes apoptosis), it penetrate
the mitochondrial membrane causing a leakage of cytochrome C from the
mitochondria.

 In the cytoplasm, the cytochrome C molecules combine together with Apaf-1

and Pro-caspase-9 in an ATP-dependent manner to form a multi-subunit
complex (Apoptosome).

 Actually the binding of Apaf-1 induces a conformational change in the Pro-

caspase-9 and activated to Caspase 9 (act as initiator in intrinsic pathway).

 The caspase 9 activates other effector caspases creating a cascade of

proteolytic activity which leads to the lysis of cell through digestion of
structural proteins of the cytoplasm and degradation of chromosomal DNA.

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The most studied cytokine to induce extrinsic pathway of apoptosis is an extracellular
messenger protein called Tumor Necrosis Factor (TNF). The TNF cytokine is
produced by the cells of the immune system in response towards the adverse
conditions like exposure to radiation, introduction of viral toxins, exposure to
elevated temperature, exposure to other toxic substances etc.

 TNF first bind to its receptor called TNFR1 (Tumor Necrosis Factor
Receptor 1) present on the plasma membrane.
 TNFR1 is a trans-membrane receptor (death receptor) with an external ligand
binding domain and a cytosolic domain (death domain).
 Binding of TNF to the TNFR1 receptor cause a conformational change in the
death domain.
 To the activated death domain, two cytosolic adaptor proteins (TRADD and
FADD) and Procaspase-8 residues are binds to form a multiprotein complex.
 This complex act on Procaspase-8 and convert it to caspase -8 (initiator
caspase).
 It activates effector caspase -3 that carry out the self-destruction process
(apoptosis) of the cell.
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 Significance of apoptosis

 Apoptosis help to maintain the homeostasis in multicellular organisms.

 Apoptosis also helps to maintain the proper body size.
 Apoptosis maintains the constancy of cell number in an organ or organism.
 Apoptotic cell death is a pre-request for the proper embryonic development.
 By the process of apoptosis, the body can eliminate unwanted cells such as:
 A cell with severely damaged DNA
 A cell with fatal mutation
 A pathogen (virus) infected cell
 Unwanted cells formed during embryonic development
 Cells that to be killed during proper neuronal architecture development
 Apoptosis also helps to kill T lymphocytes with receptors for the proteins
present on the normal cell. These T cells are produced during the embryonic
development. These dangerous T lymphocytes are eliminated by apoptotic cell
death.
 Apoptotic cell death can be pathogenic in some cases.
 Apoptosis is involved in some neurodegenerative diseases such as
Alzheimer’s, Parkinson’s disease, and Huntington’s disease by the elimination
of essential neurons.
 Failure to induce apoptosis is the main reason for most of the cancers.

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  What Causes Cancer?

The actual cause of cancer remains a mystery. The single term “cancer” refers to over 100 diseases
that affect every part of your body. Carcinogens are chemical, physical, biological, or any substances that
are agents in causing cancer. If allowed to accumulate in the human body in large amounts or for extended
periods of time, there is a higher likelihood that your cells will become damaged, resulting in the growth of
cancer cells.
 Five Primary Categories of Cancer-Causing Carcinogens

1. Tobacco Smoke: Whether you are a smoker or a victim of secondhand smoke, all scientific research
agrees that smoking is the number one cancer-causing habit. Interestingly, though, it’s not the actual
tobacco that causes cancer, but rather the chemicals used during the production of the tobacco
product. Smoking is directly linked to cancer of the lungs, esophagus, respiratory tract, bladder, and
pancreas.
2. Diet: What a person eats can also be a trigger for cancer. The Western diet is filled with fat, sugar,
and sodium, resulting in an obesity epidemic. Then there are genetically modified (GMO) foods and
chemical toxins that are found throughout the food manufacturing industry. Prevention of cancer
begins with what you put in your body. Choosing foods that feed your cells, boost your immunity,
and inhibit the growth of cancer is crucial to being passed over by this disease.
3. Pathogens: Some viruses, bacteria, and parasites can cause cancer. Hepatitis B and C, human
papillomavirus (HPV), and Epstein-Barr can be carcinogenic in the human body. Parasitic
organisms are the main cause of cancers in some developing countries. In certain regions of Asia
and Africa, the liver fluke parasite – Clonorchis sinensis – can cause liver cancer. In North Africa,
infection with the parasite Schistosoma haematobium causes bladder cancer. Sterilization of
drinking water, proper hygiene, and adequate sanitation reduces the spread of such parasites.
4. Radiation: While people who work with radioactive materials (such as X-ray technicians) have a
risk of cancer, they are not the largest portion of those diagnosed with the cancer-causing carcinogen
radiation. Too much exposure to harmful ultraviolet (UV) rays has been proven as the cause for
rapid aging, skin damage, and cancer. Skin cancer is the most diagnosed form of cancer worldwide
and the number of cases grows every year.
5. Environmental and Occupational Hazards: Air, water, and soil pollution can cause cancer in the
lungs and bladder. More cases of lung cancer are found in cities and urban areas where air pollution
levels are considered unsafe. Occupational hazards apply to people that work with known cancer-
causing carcinogens such as asbestos, lead, benzene, and vinyl chloride. Where you work and where
you live make up a large portion of your daily life. Ensuring that you minimize your exposure to
harmful toxins will lower your risk of being diagnosed with cancer.

Other Known to be Human Carcinogens

Asbestos, Benzene, Coal, Tars, Formaldehyde, Hepatitis B & C Virus, Mustard Gas, Solar Radiation,
UltravioletRadiation, Wood Dust

Top 10 Cancer Causing Foods to Cut Your Cancer Risk in Half

 Genetically Modified Foods (GMOs): The rapidly growing industry of genetically modified crops
are infiltrating our food supply at an alarming rate. More than 90% of our corn and soy are now
genetically modified. This fairly new practice is the source of many debates. Experts agree that
adequate testing was not done before GMO foods were added to the ingredient listing of thousands
of products. In other words, no one – including the growers and manufacturers of GMO foods –
knows the long-term effect they will have on human health. Look for GMO-free labels whenever
possible or buy organic (which always means a product is not genetically modified).
 Microwave Popcorn: From the chemically-lined bag to the actual contents, microwave popcorn is at
the center of lung cancer. Not only are the kernels and oil likely GMO (which the manufacturer does

1
 not have to disclose) unless organic, the fumes released from artificial butter flavoring contain
diacetyl, which is toxic to humans.
 Canned Goods: Most cans are lined with a product called bisphenol-A (BPA), which has been
shown to genetically alter the brain cells of rats. Many plastic goods, thermal paper, water lines, and
many dental composites also contain BPA. Help protect your DNA by sticking to fresh or frozen
vegetables that have no added ingredients for your family’s table! These are better for you and
available year-round.
 Grilled Red Meat: While grilled food can taste delicious, scientists have discovered that preparing
meats in this way – especially processed meats like hot dogs – releases a carcinogen called
heterocyclic aromatic amines. When you grill red meat to the point of well-done, it changes the
chemical and molecular structure of the meat. You’re better off baking, broiling, or preparing meat in
a skillet than on the grill.
 Refined Sugar: The biggest cancer causing food (by far) is high-fructose corn syrup (HFCS) and
other refined sugars. Even brown sugar is highly refined white sugar with some of the removed
molasses added back in for flavor and color. Refined sugars (and foods made with them) are the
source of major insulin spikes and feed the growth of cancer cells. Since the majority of the sugar
supply in the U.S. is made using genetically modified (GMO) sugar beets, a healthier option is
organic honey, coconut sugar, or maple sugar. Now that oncologists are using diabetes medication to
fight cancer cells, there’s no doubt (finally) that those mutated cancer cells love sugar.
 Salted, Pickled, and Smoked Foods: These products typically contain preservatives, such as
nitrates, which are intended to prolong shelf life. The additives used in processed foods can
accumulate in your body over time. Eventually, such toxins cause damage at the cellular level and
lead to diseases like cancer. When smoked foods are cooked at high temperatures, the nitrates are
converted to the much more dangerous nitrites.
 Soda and Carbonated Beverages: Sodas have been at the center of the health debate for two
decades as a major cancer causing food. Filled with high-fructose corn syrup (HFCS), dyes, and a
host of other chemicals, they are very bad for every aspect of your health. They provide zero
nutritional value and rob your body of the nutrients you get from other foods.
 White Flour: When flour is refined, all nutritional value is removed. Then it’s bleached with
chlorine gas to make it more appealing to consumers. The glycemic index for white flour is very high
– meaning it spikes your insulin levels without providing nutritional fuel. Carbohydrates are
converted to sugars by your body, so excessive products that contain white flour can lead to
increased insulin resistance. Simple sugars (like refined carbohydrates) are the preferred fuel source
for cancer.
 Farmed Fish: Commercial fish farming involves raising an incredible number of fish (such as
salmon), in a crowded environment. More than 60% of the salmon consumed in the United States
comes from a farming operation where they are treated with antibiotics, pesticides, and other
carcinogenic chemicals to try and control the bacterial, viral, and parasitic outbreaks that result from
cramming so many fish in a small space. Farmed fish also don’t have as much omega-3 as wild
salmon.
 Hydrogenated Oils: Vegetable oils are chemically extracted from their source, chemically treated,
and more chemicals are added to change the smell and taste. They’re packed with unhealthy omega-6
fats (that Americans already consume way too much of) and have been proven to alter the structure
of our cell membranes

4 Steps to Help Prevent Cancer

1. Eat organic whenever possible.
2. Choose raw or clean frozen if availability of fresh product isn’t good in your area.
3. Fill half your plate each meal with non-starchy vegetables. If you eat animal products, make sure
they’re pastured and grass-fed meats and dairy goods (including eggs). Use only high quality oils
such as coconut oil, olive oil, ghee, or grass-fed butter.
4. Cut back drastically on grains and sugars.

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 CAUSES OF CANCER

The actual cause of cancer remains a mystery. The single term “cancer” refers to over
100 diseases that affect every part of your body. Carcinogens are chemical, physical,
biological, or any substances that are agents in causing cancer. If allowed to accumulate in
the human body in large amounts or for extended periods of time, there is a higher likelihood
that your cells will become damaged, resulting in the growth of cancer cells.

Five Primary Categories of Cancer-Causing Carcinogens

 Tobacco Smoke: Smoking is directly linked to cancer of the lungs, esophagus,

respiratory tract, bladder, and pancreas.

 Diet: there are genetically modified (GMO) foods and chemical toxins that are found
throughout the food manufacturing industry. Prevention of cancer begins with what
you put in your body. Choosing foods that feed your cells, boost your immunity, and
inhibit the growth of cancer is crucial to being passed over by this disease.

 Pathogens: Some viruses, bacteria, and parasites can cause cancer. Hepatitis B and C,
human papillomavirus (HPV), and Epstein-Barr can be carcinogenic in the human
body. Parasitic organisms are the main cause of cancers in some developing countries.
Eg: liver fluke parasite – Clonorchis sinensis – can cause liver cancer, the parasite
Schistosoma haematobium causes bladder cancer. Sterilization of drinking water,
proper hygiene, and adequate sanitation reduces the spread of such parasites.

 Radiation: While people who work with radioactive materials (such as X-ray
technicians) have a risk of cancer, they are not the largest portion of those diagnosed
with the cancer-causing carcinogen radiation. Too much exposure to harmful
ultraviolet (UV) rays has been proven as the cause for rapid aging, skin damage, and
cancer. Skin cancer is the most diagnosed form of cancer worldwide and the number
of cases grows every year.

 Environmental and Occupational Hazards: Air, water, and soil pollution can cause
cancer in the lungs and bladder. More cases of lung cancer are found in cities and
urban areas where air pollution levels are considered unsafe. Occupational hazards
apply to people that work with known cancer-causing carcinogens such as asbestos,
lead, benzene, and vinyl chloride. Where you work and where you live make up a
large portion of your daily life. Ensuring that you minimize your exposure to harmful
toxins will lower your risk of being diagnosed with cancer.

Top 10 Cancer Causing Foods to Cut Your Cancer Risk in Half


Genetically Modified Foods (GMOs): The rapidly growing industryof genetically
modified crops are infiltrating our food supply at an alarming rate. More than 90% of
our corn and soy are now genetically modified. This fairly new practice is the source
of many debates. Experts agree that adequate testing was not done before GMO foods
were added to the ingredient listing of thousands of products

1

Microwave Popcorn: From the chemically-lined bag to the actual contents,
microwave popcorn is at the center of lung cancer. Not only are the kernels and oil
likely does not have to disclose) unless organic, the fumes released from artificial
butter flavoring contain diacetyl, which is toxic to humans.

Canned Goods: Most cans are lined with a product called bisphenol-A (BPA), which
has been shown to genetically alter the brain cells of rats. Many plastic goods, thermal
paper, water lines, and many dental composites also contain BPA.
 Grilled Red Meat: While grilled food can taste delicious, scientists have discovered
that preparing meats in this way – releases a carcinogen called heterocyclic aromatic
amines. When you grill red meat to the point of well-done, it changes the chemical and
molecular structure of the meat.

Refined Sugar: The biggest cancer causing food (by far) is high-fructose corn syrup
(HFCS) and other refined sugars. Even brown sugar is highly refined white sugar with
some of the removed molasses added back in for flavor and color. Refined sugars (and
foods made with them) are the source of major insulin spikes and feed the growth of
cancer cells.

Salted, Pickled, and Smoked Foods: These products typically contain preservatives,
such as nitrates, which are intended to prolong shelf life. The additives used in
processed foods can accumulate in your body over time. Eventually, such toxins cause
damage at the cellular level and lead to diseases like cancer. When smoked foods are
cooked at high temperatures, the nitrates are converted to the much more dangerous
nitrites.

Soda and Carbonated Beverages: Sodas have been at the center of the health debate
for two decades as a major cancer causing food. Filled with high-fructose corn syrup
(HFCS), dyes, and a host of other chemicals, they are very bad for every aspect of
your health. They provide zero nutritional value and rob your body of the nutrients you
get from other foods.
 White Flour: When flour is refined, all nutritional value is removed. Then it’s
bleached with chlorine gas to make it more appealing to consumers. Carbohydrates are
converted to sugars by your body, so excessive products that contain white flour can
lead to increased insulin resistance. Simple sugars (like refined carbohydrates) are the
preferred fuel source for cancer.

Farmed Fish: Commercial fish farming involves raising an incredible number of fish
(such as salmon), in a crowded environment. More than 60% of the salmon consumed
in the United States comes from a farming operation where they are treated with
antibiotics, pesticides, and other carcinogenic chemicals to try and control the
bacterial, viral, and parasitic outbreaks that result from cramming so many fish in a
small space. Farmed fish also don’t have as much omega-3 as wild salmon.
 Hydrogenated Oils: Vegetable oils are chemically extracted from their source,
chemically treated, and more chemicals are added to change the smell and taste.
They’re packed with unhealthy omega-6 fats (that Americans already consume way
too much of) and have been proven to alter the structure of our cell membranes.

2
 Genetics of Cancer
The abnormalities in cancer cells usually result from mutations in protein-
encoding genes that regulate cell division

The genes that involve in the cancer can be divided into following types.

 Protooncogenes

A protooncogene is a normal gene found in the cell. There are many proto-
oncogenes. Proteins encoded by protooncogenes may function as growth factors or
their receptors, signal transducers, transcription factors or cell cycle components.
Protooncogene products regulate the cell growth, division of cells, prevent cell
differentiation and regulate apoptosis.

Example of Proto oncogenes

RAS, Wnt, Myc, Fos/Jun, RTK, Her2 gene etc

Products of proto oncogenes genes are essential for cell survival and growth.
Mutation in protooncogenes increases the production of these proteins, thereby leading
to unregulated cell division, increased inhibition of cell death. These are the common
features of cell that have become cancerous.

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 For example, Mutations in RAS gene cause the signaling pathway to remain
“on,” leading to uncontrolled cell growth. About thirty percent of tumors including

lung, colon, thyroid, and pancreatic carcinomas - have a mutation in RAS.

 Viral Carcinogenesis

There are two classes of tumour viruses: RNA viruses and DNA viruses.
RNA virus: infect competent cells. Their RNA is converted into DNA that
incorporated into the host genome. Example of retrovirus: lymphotropic virus (HTLV-
1) and Rous sarcoma virus (RSV). Rous Sarcoma Virus (RSV) is of historical
importance, because it was the first tumour-inducing virus to be studied. RSV is a
retrovirus with a single-stranded RNA genome and its DNA copy is integrated into a
specific site of the host chromosome as a provirus. Research on RSV revealed
identification of a cancer-inducing gene (an oncogene) in RSV genome. This gene,
called src, is not essential for viral replication, as it does not code for any viral
proteins.

DNA viruses: Several DNA viruses are specific in human cancers: human papilloma
virus (HPV) , hepatitiss B virus (HBV), Epstein-barr viruses, Kaposi sarcoma virus
(KSV) . If a protooncogene under goes a somatic mutation, control of cell growth is
lost in the cell in which the mutation occurs and cancer can occur. Those
protooncogene which have been shown to mutate in any individual are called cellular
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oncogenes and are designated by the prefix "c" (i.e. c-myc, c-abl) to distinguish them
from the viral oncogenes.

 Tumor Suppressor Genes

The proteins made by tumor suppressor genes normally inhibit cell growth,
preventing tumor formation. Mutations in these genes result in cells that no longer
show normal inhibition of cell growth and division. The products of tumor suppressor
genes may act at the cell membrane, in the cytoplasm, or in the nucleus. Mutations in
these genes result in a loss of function (that is, the ability to inhibit cell growth).

5
 Treatment of Cancer:

Cancer is curable, if it is detected at the early stages. The patient enjoys full life
without recurrence of the disease.

Cancer is treated in three ways:

(i) Surgery: Some of the infected organs are removed from the body by surgery:
Example-Uterus, breast etc.

(ii) Radiotherapy: The affected organs are irradiated to kill the cancerous cells and
prevent them from spreading.

(iii) Chemotherapy: Strong chemicals are used to kill the cancerous cells and isolate
these cells from other organs. Sometimes all these three methods are applied to cure
cancer. This dreaded disease can be cured fully, if it is detected at the preliminary
stage. So social consciousness should be developed for early detection.