Unit 9: An Introduction to Cancer

Cancer: According to the American Cancer Society cancer is the name given
to a collection of related diseases where some of the body’s cells begin to
divide without stopping (uncontrolled cell division) and spread into surrounding
tissues.

So there are two important features related to cancer:

1. Uncontrolled Cell Division and growth
2. Spreading

Neoplasm/Tumor: An abnormal mass of tissue that forms when cells grow and
divide more than they should (uncontrolled cell divisions and growth) or do not
die when they should.

There are three main types of tumor:

Benign: These are not cancerous. They either cannot spread or grow, or they do

so very slowly. If a doctor removes them, they do not generally return.

Premalignant: In these tumors, the cells are not yet cancerous, but they have

the potential to become malignant.

Malignant: Malignant tumors are cancerous. The cells can grow and spread to

other parts of the

body.

It is not always clear how a tumor will act in the future. Some benign tumors can

become premalignant and then malignant. For this reason, it is best to monitor

any growth.

Primary and Secondary malignant tumors

In medical lingo, "primary" refers to the original site of the malignant tumor.
"Secondary" refers to any additional sites where the cancer has spread.
Cancer cells vs Normal cells

Cancer cells Normal cells

Cell shape is irregular Cell shape is regular

Uncontrolled cell growth and division Controlled cell growth and division

Cancer cells are able to bypass Immune cells can recognize and
immune cells destroy damaged normal cells

Required high amount of glucose Relatively low amount of glucose is

required

Tumor angiogenesis is observed No such angiogenesis is observed

Tumor angiogenesis

Angiogenesis is the physiological process through which new blood vessels form from
pre-existing vessels

Tumor angiogenesis is defined as the proliferation/formation of a network of blood

vessels from the pre-existing blood vessels. In this way a tumor (malignant tumor cells)
will have a supportive microenvironment rich with oxygen and nutrients to sustain
optimal growth.

Tumor angiogenesis is also responsible for the spreading of malignant tumor cells at the
distant parts of the body, a process which is also known as metastasis.
Metastasis

Metastasis is the spread of cancer cells to new areas of the body, often by way
of the lymph system or bloodstream. Spreading through the bloodstream is
known as hematogenous spread whereas spreading through the lymph node is
known as lymphatic spread.

A metastatic cancer, or metastatic tumor spread from the primary site of

origin (where it started) into different areas of the body (secondary site).
Tumor that formed at the secondary site is known as secondary tumors.
The cancer may have spread to areas near the primary site, called regional
metastasis, or to parts of the body that are farther away, called distant
metastasis. These secondary tumours – metastases – are responsible for almost
90% of cancer-related deaths.
This capacity of tumour cells to invade and metastasize is one of the hallmarks
of cancer. Metastasis enables tumours to survive and grow in new environments
where there are no restrictions of space or nutrients. The newly
formed secondary tumours can contain cancer cells and also some normal
support cells recruited from host tissue.

Stages of metastasis:

The migration of cancer cells from the primary location to a distant site (secondary
site) is a complex biological process that involves changes at the molecular, cellular and
physical level. Briefly, the metastasis process involves following stages:
 1. Local invasion: Malignant tumor cells detached from the primary site and start
invading nearby tissues.
2. Intravasation: The malignant tumour cells now enter into the blood vessels or
lymph vessels. This is a critical step in this pathway and it involves a complex,
morphological change, wherein the cancer cell acquires properties of
invasiveness and cell motility. This enables the cancer cell to push its way
through the capillary wall and into the circulatory system.
3. Transport: Cancer cells travel through the blood or lymph until they anchor to a
solid supporting tissue. At this stage they also need to survive from the immune
response (Known as immune escape)
4. Extravasation: In this step migratory malignant tumor cells within the blood or
lymphatic vessels will invade the other tissues (secondary site) which is distant
from the primary site.
5. Colonization: Development of secondary malignant tumor at the secondary site

Molecular Basis of Cancer

Genetic changes and Cancer risk

Cancers are caused by a change in, or damage to, one or more genes. Most changes in a
gene are because of a gene mutation. Mutations can stop genes from working properly.
Genes that have mutations that are linked to cancer are sometimes called cancer genes.

It takes more than one gene mutation for a cell to become cancerous. Researchers have
been able to link some types of cancer to certain gene mutations. But there are also
cancers where we don’t know which gene mutations cause them.

Genes related to the cancer (Cancer genes)

There are 3 main types of cancer genes that control cell growth and can cause cancer
to develop.

Proto-Oncogenes: Proto-oncogenes are normal genes that control cell growth but if
they become mutated they can turn into oncogenes which lead to the cancer.
Proto-oncogenes and oncogenes act like on/off switches. A proto-oncogene is usually
switched off. When a proto-oncogene is switched on, it is telling a cell to grow or
divide. But oncogenes are always switched on – so its cells grow out of control.

Example: BRAF gene, ERBB2 gene

Tumour suppressor genes: Tumor suppressor genes are normal genes that
control/slowdown cell growth and division, repair mistakes in DNA and tell cells when to
die (a normal process called apoptosis or programmed cell death). They help protect us
against cancer. Tumour suppressor genes are working properly when they are switched
on. They prevent cells from dividing too quickly. But when these genes are mutated,
they are turned off. This causes cells to grow out of control which can lead to cancer.

Example: BRCA gene, p53 gene, APC gene

DNA repair genes: DNA repair genes fix mistakes in other genes that can happen
when DNA is copied. When DNA repair genes are mutated, they can’t fix mistakes in
oncogenes and tumour suppressor genes, and this can lead to cancer.

So, Cancer is a genetic disease—that is, cancer is caused by certain changes (mostly
mutation) to genes that control the way our cells function, especially how they grow and
divide.

Most of the time cancer is sporadic, i.e, happens by chance or not hereditary. In
sporadic type of cancer it occurs in people who do not have a family history of that
cancer

Carcinogen: Carcinogen is any substance, radionuclide, or radiation that

promotes carcinogenesis i.e., the formation of cancer.

Carcinogens are capable of initiating the development of malignant tumours by

inducing cellular genetic changes.

Causes of Cancer

1. Lifestyle factors: Excessive smoking, alcohol consumption etc.

2. Radiations: Regular exposure to ionizing radiation (X-rays) or non-ionizing
radiation (UV-rays).
3. Malfunction of genes: Genes like Tumor suppressor genes
 4. Viruses: Retroviruses can cause cancer. Example: Epstein-Barr virus
(EBV)
5. Environmental factors : Use of carcinogenic pesticides or fertilizers in
the farming
6. Family history: If mutation is there in the sperm or egg cells in any of
genes responsible for control of cell division

Ten hallmarks of cancer

1. Growth signal autonomy: Cancer cells can divide without the external

signals normally required to stimulate division.

2. Insensitivity to growth inhibitory signals: Cancer cells are unaffected

by external signals that inhibit division of normal cells

3. Evasion of apoptosis: When excessive DNA damage and other

abnormalities are detected, apoptosis (a type of programmed cell

death) is induced in normal cells, but not in cancer cells.

4. Reproductive potential not limited by telomeres: Each division of a

normal cell reduces the length of its telomeres. Normal cells arrest

further division once telomeres reach a certain length. Cancer cells

avoid this arrest and/or maintain the length of their telomeres.

5. Sustained angiogenesis: Most cancers require the growth of new blood

vessels into the tumor. Normal angiogenesis is regulated by both

inhibitory and stimulatory signals not required in cancer cells.

6. Tissue invasion and metastasis: Normal cells generally do not migrate

(except in embryo development). Cancer cells invade other tissues

including vital organs.

7. Deregulated metabolic pathways: Cancer cells use an abnormal

metabolism to satisfy a high demand for energy and nutrients.

8. Evasion of the immune system: Cancer cells are able to evade the

immune system.

9. Chromosomal instability: Severe chromosomal abnormalities are found in

most cancers.

10. Inflammation: Local chronic inflammation is associated with many types

of cancer.
Types of cancer

Symptoms of cancer

1. Persistent cough or blood-tinged saliva

2. A change in bowel habits
3. Blood in the stool
4. Unexplained anemia
5. Lump in any tissues
6. A change in urination

Detection of Cancer
Treatment of Cancer
Common treatment Strategy included:

(1) Surgery: Remove the malignant tumor.

(2) Radiation therapy: High doses of radiation to kill the cancerous cells
(3) Chemotherapy: Chemicals/drugs to kill cancer cells. Example is cisplatin
(4) Stem cell therapy: Bone marrow replacement in Leukemia