Cancer biology

Cancer is a proliferation of cells which grow in an uncontrolled manner, invading local tissues and spreading widely through the blood or lymphatics to produce secondary deposits, or metastases in distant parts of the body.

The word ‘cancer’ comes from Latin, meaning a crab. A tumour was called a cancer because of swollen veins around the area resembling a crab’s limbs. The study of cancer is called Oncology. Oncology is a word derived from the Greek, onchos, a lump, or tumour. The abnormal tissue growth is called neoplasm. If a neoplasm can cause harm by spreading, it is said to be malignant.

Cancer was known to ancient civilizations. However the disease as it would be defined today was established as an entity by German pathologists of 19th century. They described cellular nature of cancer and classified cancer. At the beginning of the 20th century, most major forms of cancer had been described. Further, attention was focused on finding the cause and introducing treatment. In 1775 Pott recognized cancer in chimney sweeps. He associated soot with cancer. From this time onwards environmental and occupational hazards were recognized as follows:

Shale oil                                     skin cancer in workers

Radioactive ores                        lung cancer in miners

Beta-naphthylamine                   bladder cancer in rubber industry workers

Cigarettes                                    lung cancer

Later it was discovered that certain viruses can also cause cancer. One of the earliest viruses, causing cancer, described was Rous sarcoma virus. Recently, human T-cell leukemia has been found to be due to the virus HTLV-1.

Some forms of cancer can also be inherited. A rare eye tumour, retinoblastoma is inherited. It is a dominant character showing Mendelian in­heritance.

Cancer biology

The knowledge of cancer biology is growing rapidly. Researches are being conducted to fully understand the development of cancer at the cellular or molecular level. The available information is not sufficient for satisfactory treatment of cancer. 

. During normal development and growth the cells in our body divide mitotically and get differentiated to specialized cells of the tissues. The processes of cell mitosis, growth and differentiation are controlled by cellular genes. Cancer is caused due to mutation or abnormal activation of such genes. Such a mutation can happen in a single cell. Thus it may be monoclonal in origin. With further growth of cancer, additional mutations may occur in the daughter cells giving rise to subclones. The mutated cells may remain as heterogeneous cancer cells. Among these subclones some may have greater capacity and metastasize to distant tissues. They may also remain more resistant to damage from various anticancer treatments.

The cancer cells have characteristic properties. They can be differ-entiated from normal cells under microscopic observation. These cells have large nuclei. In each cancer cell, the ratio of nucleus to cytoplasm is high. They have prominent nucleoli. The cells can grow indefinitely in culture medium. As component cell of a tissue they remain less differentiated. Even after getting organized into tissues unlike other cells they do not lose their replicative capacity. Cancer cells have the ability to invade surrounding tissues.

The sequence of events that convert a normal cell into a cancer cell is called carcinogenesis. The process of carcinogenesis includes initiation, growth, promotion, conversion, propagation and progression. Progression includes the processes of invasion and metastasis.

Mature cancers have relatively uncontrolled growth, behaviour. As other normal cells they do not show any of the normal intracellular and extracellular growth control mechanisms. Initially the cancer cells have an exponential growth. Gradually their growth surpasses blood vascular supply. This results in slowing down of growth.

Molecular biology of cancer

Techniques in molecular biology have helped in understanding the most intimate structure of the cancer cell. It has been found that at molecular level two mechanisms operate.

1-The parts of genome involved in cell growth become activated. These are called the ‘proto-oncogenes’. These strands of DNA induce malignant growth transformation in the cells. The conversion of proto-oncogenes into oncogenes can happen due to ‘point mutations’ on DNA. Further such cancer cells dis play chromosomal abnormalities such as duplication, deletions and translocations. Thus such alterations in gene arrangement can lead to generation of oncogenes.

Oncogenes of human tumours

Oncogene           Type of cancer                          Activation mechanism

hox11                    Acute T-cell leukemia                  Translocation

ErbB-2                  Breast and ovarian carcinomas      Amplification

L-myc                  Lung carcinoma                              Amplification

Ret                        Thyroid carcinoma DNA                 rearrangement

A distinct mechanism by which oncogenes are activated in human tumors is amplification. It results in elevated gene expression. Gene amplification is very common in cancer cells. It occurs a thousand times more frequently than in normal cells. Molecular biologists are now working on the products of oncogenes.

2-The growth of normal cells is controlled by suppressor genes. In cancer, parts of the genome functioning as the suppressor gene are either lost or inactivated. Hence, negative regulators of cell proliferation are removed. It contributes to the abnormal proliferation of cells.

Gene                           Type of cancer

APC                            Colon / rectum carcinoma

BRCA 1                     Breast and ovarian carcinoma

NK 4                        Melanoma, lung carcinoma,1

                               brain tumors, leukemias, lymphoma  

Rb                          Retinoblastoma

PTEN                    Brain tumors, kidney and lung carcinomas

The protein products of the tumor suppressor genes normally inhibit cell proliferation. Inactivation of such genes therefore leads to tumor development.

The complete sequence of events required for the development of any human cancer is not yet known. But it is clear that both the activation of oncogenes and the inactivation of tumor suppressor genes are critical steps in tumor initiation and progression. Simultaneous effect on both the genes will result in multiple genetic defects. It results in the increased proliferation, invasiveness and metastatic potential of cancer cells.

Types of cancer

Cancers are named according to the tissues from which they arise.

1-Sarcoma - Malignancy in structural tissues Ex: Osteosarcoma (bones) liposarcoma (fa)

2-Carcinoma - Epithelial cancers. Ex: Lung carcinoma, breast carcinioma

3-Lymphoma - Lymphatic tissues

4-Leukemia - White blood cells

Causes for Cancer (Etiology)

Majority of the cancers are caused by living habits and environmental

Factors.

1-Tobacco: - Nearly 35% of all cancer deaths are due to usage of tobacco in some form. At least 90% of lung cancer deaths are due to smoking. Smoking can also affect gastro-intestinal tract, pancreas, genitourinary tract and upper respiratory passage. Snuff and chewing tobacco can affect mouth and respiratory tracts. Smoke inhaled by non-smokers (passive smoke) can also cause lung cancer and blood cancer.

2-Exposure to ionizing radiations such as x-rays, gamma rays, uv rays can produce cancer. These radiations rupture DNA strands, causing mutations. Solar radiations can cause skin cancers.

3-Physical irritants, such as continued abrasion of the linings of the intestinal tract by some types of food can also lead to cancer. Dietary substances such as fat, high calorie intake of animal proteins, salted or smoked food can cause cancer in Breast, Colon, Stomach and Oesophagus.

4-Certain drugs if taken without medical advice can cause cancer.

5-Viruses and parasitic organisms like schistosoma, liver fluke can also affect.

Cancer and death

A severe onset of cancer ends in the death of a person. It is because of the unique characteristics of the cancer cells. The growth of normal cells is controlled by certain factors. However the cancer cells do not require the growth factors. Hence these cells do not respect usual cellular growth limits.

Normal cells have a nature of remaining together in tissues. But the cancer cells are less adhesive to each other. Hence they wander through the tissues and enter the blood. They can be transported to all parts of the body and cause new cancer growths.

The cancer cells rapidly multiply. Some cancers also produce angio­-genic factors that cause many new blood vessels to grow into the cancer. Thus these cells will drain all the nutrients and normal cells get deprived of food. Ultimately the normal cells and tissues suffer nutritive death.

Management of cancer

The treatment or management of cancer depends on an accurate di­agnosis. Diagnosis is made through microscopic observations (tissue biopsy), study of markers on the surface of cells, cytochemical methods, cytogenetic and various scanning and ‘x’ ray diagnostic methods.

In order to compare results and for communicating treatment programme among medical personnel staging systems are essential (Ex: stage1, stage2) staging defines tumours as either confined to the tissue of origin or having spread to local tissues and organs and finally as having metastasized.

After diagnosis, treatment of cancer involves surgery, chemotherapy, radiotherapy and hormonal treatments.

Till last century, surgery was the only effective method of treatment. Even to-day through surgery biopsy can be effected for diagnosis. If the tu­mour is restricted to the primary site, through surgery it can be removed. In latest treatment procedures surgery is restricted to affected region, rather than amputation or removal of the entire organ.

Radiotherapy: - Discovery of x-rays by Roentgen(1895) and of radioactivity by Curies in 1899 opened new ways of treating cancer. In Radiotherapy high energy ionizing radiations are used. The radiations used are x-rays and gamma rays or subatomic particles such as beta particles, high energy electrons and neutrons or charged particles like helium ions. Ionizing radiations can penetrate tissues. They can damage DNA leading to cell death and mutagenesis. The basis of radiation therapy depends on the differential sensitivity of the tumour tissue and the normal tissue. Hence the aim of radiotherapy is to prescribe sufficient radiation dose to the tumour, sparing as much of the normal tissue as possible.

Chemotherapy: - The purpose of chemotherapy is to prevent cancer cells from multiplying, invading and metastasizing. The chemicals used in treatment affect cell multiplication and tumour growth. Several drugs are now available for usage. They can use singly or in combination. Some cancers like breast cancer are hormone dependent. Hence hormones are used in their manage­ment.

Inspite of all advances in diagnostics and treatment, the death rate due to cancer is greater. Primary prevention of cancer will be a better alternative to diagnosis and treatment. 70% to 80% of cancers result from environmental causes. Hence public awareness towards environmental issues is a need. 33% of cancers in India are tobacco related. Hence smoking cessation and other measures to reduce tobacco usage are to be insisted upon. Consumption of fibrous food and avoidance of fatty food will avoid tumours related to alimentary canal.

Thus it is apparent that fight against cancer will be successful with early detection and appropriate education for avoidance.

References

T. Sargunam Stephen, Biology (Zoology). First Edition – 2005, Government of Tamilnadu.