Cancer

During the development of cancer, tumor invades nearby tissues by breaching the basement membrane.
Basement membrane is a sheet of proteins and other substances to which epithelial cells adhere and form a barrier between tissues.
Once tumor breaks this membrane, cancerous cells invade surrounding tissue and the blood stream via lymphatic vessels and discharge contents into the blood.
Tumor cells that invade lymphatic vessels become trapped in lymph nodes.
Cells that gain access to blood vessels are disseminated to various parts of the body, bones, lungs and brains
At distant sites, cancer cells form secondary tumors, or metastases.
Ability to metastasize makes cancer a lethal disease.
Primary tumor can be controlled by many available therapies.
It is the disseminated disease that proves fatal to the host eventually.

Top

Malignant and Benign Tumors

Tumors are classified as either being benign or malignant based on whether they can spread by invasion and metastases.

Source: www.cancer.gov

Benign tumors cannot spread by invasion and metastases. They grow locally.
Malignant tumors are capable of spreading by invasion and metastases.

Microscopic Appearance of Cancer Cells

Top

Normal
Cancerous

Source: www.cancer.gov

What causes Cancer?

Top

How is Cancer detected?

Top

Change in bowel or urine habits
A sore throat that does not heal
Unusual bleeding or discharge
Thickening of lump in breast or elsewhere
Indigestion or difficulty in swallowing
Obvious change in warts or moles
Nagging cough or hoarseness

Cancer Screening

Cervical Cancer Screening	PAP test
Breast cancer screening	Mammogram
Prostrate and ovarian cancer screening	PSA test
Colon cancer screening	Fecal occult blood test

Biopsy

When preliminary symptoms, PAP test, mammogram, PSA test, FOBT/colonoscopy indicate possible existence of cancer, biopsy is performed.
Biopsy is surgical removal of a small piece of tissue for microscopic examination.

For leukemia, small blood sample serves the purpose.

Source: www.cancer.gov

Microscopic examination reveals the presence of malignant/benign tumors.
Micro arrays determine the genes responsible.
Proteomic profiles analyze the protein activity.

Tumor Grading

Top

Microscopic examination reveals information regarding behavior of tumor and its response to treatment.
Cancer with more number of highly dividing cells tend to grow more quickly, spread faster to other organs and are less responsive to therapy when compared to cancers which have a normal appearance.
Based on these differences under a microscope, doctors assign a numerical grade to cancer. Low number grade (I & II) refers to cancers with fewer cell abnormalities than those with higher numbers (III & IV).

Tumor Staging

Tumor staging is done, once cancer has been diagnosed to determine how far the disease has progressed. Commonly asked questions are :

How large is the tumor and how deeply has it invaded the surrounding tissue.
Have cancer cells spread to regional lymph nodes?
Has cancer metastasized to other regions of the body?

Source: www.cancer.gov

Based on the answers to these queries, cancer is assigned a stage. Patient’s chances for survival are better when cancer is detected at a lower stage.

Genes and Cancer

Top

Chemicals, radiation, viruses and heredity all contribute to the development of cancer by triggering changes in cell’s genes.
Chemicals and radiation act by damaging genes.
Viruses introduce their own genes into cells.
Heredity passes on alterations in genes that make a person susceptible to cancer

Genes are a set of inherited instructions that lie within a person’s chromosome.

Source: www.cancer.gov

Genes are mutated in various ways as part of the mechanism by which cancer arises.

Source: www.cancer.gov

The simplest type of mutation involves a change in a single base along the base sequence.
Sometimes large segments of DNA molecule are accidentally repeated, deleted and moved.

Molecular basis of cancer

Top

The genes that regulate the growth of cells can be divided into two categories :
1. Proto-oncogenes which encourage cell growth
2. Tumor suppressor genes which inhibit it
3. DNA repair genes

Proto-oncogenes

Proto-oncogenes and normal cell growth

Source: www.cancer.gov

Many of the agents known to cause cancer (chemicals, viruses and radiation) exert their effects by inducing changes in these genes or by interfering with the function of the proteins encoded by these genes.

Oncogenes are mutant proto-oncogenes

Source: www.cancer.gov

Mutations in proto-oncogenes give rise to oncogenes that tend to over stimulate cell growth, keeping the cell active, when it should be at rest.

Tumor suppressor genes

A second group of genes implicated in cancer are the tumor suppressor genes. Tumor suppressor genes are normal genes whose absence can lead to cancer. If a pair of tumor suppressor genes are either lost from a cell or inactivated by mutation, their functional absence might allow cancer to develop. Mutations in tumor suppressor genes eliminate necessary brakes on cell growth keeping the cell constantly active.

Source: www.cancer.gov

The RB and p53 genes

Two of the most common tumor suppressor genes are RB and p53.
The RB gene is associated with retinoblastoma, a cancer of the eye. The gene is also associated with bone tumors of children, cancers of breast, prostrate, lung, uterine, cervix and bladder in adults.
The p53 is the most commonly mutated gene in tumors. Practically every person who inherits a mutated copy of the tumor suppressor gene will develop some form of cancer.
One particular tumor suppressor gene codes for a protein called “p53”. In cells that have undergone DNA damage, the p53 protein acts like a brake pedal to halt cell growth and division.
If the damage cannot be repaired, the p53 protein eventually initiates cell suicide (apoptosis).

Source: www.cancer.gov

p53 tumor suppressor protein triggers apoptosis

DNA repair genes

A third type of genes implicated in cancer are called “DNA repair genes”.
DNA repair genes code for proteins whose normal function is to correct errors that arise when cells duplicate their DNA prior to cell division.
Mutations in DNA repair genes can lead to failure in repair, which in turn allows subsequent mutations to accumulate.

Cancer tends to involve multiple mutations.
Cancer may begin because of the accumulation of mutations involving oncogenes, tumor suppressor genes and DNA repair genes.

Treating Cancer

Surgery

The physical removal of cancerous growth.
Most successful type of treatment.

Chemotherapy

Use of cell-killing drugs.
Tends to kill fast-growing cells (including hair, skin).

Radiation

Gamma or X-rays directed at tumors.
Kills or stuns growth of cancer cells.
Radiation “seeds” are placed onto tissue.

Cancer Prevention

Top

Avoid carcinogenic chemicals, carcinogenic radiation and cancer viruses or bacteria
Avoid tobacco
Protection against excessive exposure to sunlight
Limit alcohol and tobacco
Diet: limit fats and calories; consume fruits and vegetables
Avoid cancer viruses
Avoid carcinogens at work

The Cancer Genome Project

Top

All cancers occur due to abnormalities in DNA sequence.
Throughout life, the genome within cells of human body is exposed to mutagens and suffers mistakes in replication.
These corrosive influences result in progressive, subtle divergence of the DNA sequence in each cell from that originally constituted in the fertilized egg.
Occasionally, one of these somatic mutations alters the function of a critical gene, providing growth advantage to the cell in which it has occurred and resulting in the emergence of an expanded clone derived from the cell.
The identification of genes that are mutated and hence drive oncogenesis has been a central aim of cancer research since the advent of recombinant DNA technology.
Cancer genome project is using the human genome sequence, mutation and deletion techniques to identify somatically acquired sequence variants/mutations and hence identify genes critical in the development of human cancers.