History of Cancer

A hundred year ago, cancer was not so common but its incidence is rising alarmingly since last couple of decades, probably due to our changing lifestyle & habits. The situation is so alarming that every fourth person is having a life time risk of cancer. We are exposed to various cancer causing agents, known as carcinogens, in the food we eat, in the water we drink and in the air we breathe. Our single meal may contain a dozen of carcinogens in the form of residues of pesticides and insecticides. Other major causes of cancer include exposure to nuclear radiation, ionising radiation, particle radiation emitted by radioactive substances, solar radiation and electromagnetic radiation emitted by many manmade devices including computers, cell phones etc. and nutritional imbalance in our diet such as fast foods. Likewise there is a long list of chemical, physical, biological and geographical carcinogens. Moreover, the modern life is full of stress that further enhances the risk of cancer by suppressing immune system of the body.

Cancer is not a single disease rather it is a general term used to describe various malignant tumours that can affect all forms of higher organisms including plants and animals. More than a hundred types and sub types of cancer are known to affect the human beings. Cancer can be defined as an abnormal growth of cells in any tissue or organ of the body and these cells have a tendency to spread & grow in other parts of the body. Cancer preys on the host and continues to grow indefinitely competing with normal cells of the body for nutrition.

Cancer had its origin since the evolution of multicellular organisms. Our knowledge of cancer goes back to the dawn of civilisation. The evidence of cancer has been found in skeletons of pre historic animals and Egyptian mummies. The earliest written records on cancer have been traced back to the ancient Indian, Egyptian and Greek writings. The word Cancer has its origin from the Latin word Cancrum (Greek: Karkinos), which means crab. Ancient Indian surgeon, Sushruta, used to cauterise the malignant tumours with red hot iron rods and had described various types of malignant tumour in his text ‘Sushruta Samhita’ written in circa 600 B.C. Similarly ancient Egyptians tried fire drill to treat cancer. It is believed that the Greek surgeon, Leonides, was the first to operate upon cancer with a knife.

‘What causes cancer’ had been the most debatable topic in the history of medicine. After a prolonged era of confusion over the genesis of cancer, it was finally clear by the end of twentieth century that cancer is caused by mutations in growth regulatory genes & pathways. Robert Weinberg & Douglas Hanahan published an article ‘The Hallmarks of Cancer’ in January 2000 explaining how a normal cell is transformed into a cancer cell by activation of oncogenes, inactivation of tumour suppressor genes, dysregulation of certain pathways, evasion of apoptosis, acquisition of tumour angiogenesis, acquisition of ability to migrate, invade and colonise in other tissues & organs of the body.

Normal cell division in our body is a highly regulated mechanism, controlled by genes, made up of deoxyribonucleic acid (DNA) through growth regulatory pathways. Prolonged exposure to carcinogens damages the DNA and induces mutations in growth regulatory genes including oncogenes (ras, N-myc, c-myc, HER-2/neu, etc), tumour suppressor genes (p53, Rb, Ret, WT-1, NF-1, NF-2, APC, DCC, etc) and pathways (ras, Rb, myc, etc) leading to loss of control over normal cell division.

Immune cells of the body normally recognise & kill these mutated, abnormal cells. This work is executed by cytotoxic T lymphocytes (T cells), natural killer (NK) cells, lymphokine activated killer (LAK) cells and macrophages. The immune cells also produce anticancer agents, known as cytokines (Lymphokines and Monokines) including interleukins (IL-1 to IL-15), interferons (alpha, beta and gamma), tumour necrosis factors (TNF) and colony stimulating factors (CSF) and eliminate newly formed cancerous cells, when they are a few in number.

Carcinogenesis is a multi step process. A large number of carcinogens have mutagenic activity, however all the mutagens are not carcinogenic. The sub optimal dose of a carcinogen may only alter the affected cell. This altered cell is known as ‘initiated cell’ which has the highest risk of becoming cancerous. Further exposure of the same carcinogen or certain other substance (which may or may not be a carcinogen) can transform the initiated cell to the cancerous cell. The substance that transforms an initiated cell to the cancerous cell is called ‘tumour promoter.’ Although almost every living cell in the human body has the potential to become cancerous, but the malignant transformation is considered as the ‘rarest of rare’ event.

Transformation of a normal cell to a cancerous cell is probably not such a critical event in the genesis of cancer rather it is the inability of immune cells of the body to recognise and destroy these abnormal mutated newly formed cancerous cells. This has been observed that the incidence of cancer is much higher in those persons, whose immune system is suppressed due to any factor including under nutrition, old age, chronic debilitating disease and abuse of drugs such as analgesics, antibiotics, corticosteroids, etc. The risk of cancer is manifold in people affected with HPV, HIV and other viral infections including Hepatitis B & Hepatitis C. Moreover, the life has become fast & competitive from ‘cradle to grave’ generating a lot of stress that further enhances the risk of cancer by producing stress hormone (cortisone), which suppresses immune system of the body, leading to genesis of cancer.

Ultimately, only a fraction of the cancerous cells, which escape the vigil of immune cells go haywire and proliferate indiscriminately usually forming a mass, known as a neoplasm or a malignant tumour or in simple words, a cancer. As the time passes and with further exposure to carcinogens the cancer cells gain more mutations and acquire more malignant characteristics such as ability to invade & move into the adjoining tissues, penetrate into lymph & blood vessels or body cavities and travel through the respective channels to lodge themselves in various tissues & organs of the body to form new colonies or secondary growths, known as metastases. Some types of cancer spread by implant or seeding into the body cavities, while some other have the propensity to invade the veins and grow in a snake like fashion within the vein to reach up to the heart. As the disease progresses, the cancer cells accumulate more mutations and become more aggressive as they acquire the capability to create their own blood vessels (tumour angiogenesis), evade the process of programmed cell death (apoptosis) and acquire the ability of limitless replication, making cancer cells immortal.

By the time most of the cancers are diagnosed, they have already added many mutations, for example acute lymphocytic leukaemia is found to have 5 to 10 mutations at the time of diagnosis. Pancreatic cancer has shown 50 to 60 mutations while breast & colon cancers have 50 to 80 mutations at the time of diagnosis. Similarly most of the cancers have 11 to 15 aberrant (mutated) pathways by the time of diagnosis. Frequent exposure to X-rays, Gamma rays and radioactivity of contrast material used in imaging techniques, such as CT scan, PET scan, Bone scan, etc. may add further mutations, making the cancer more aggressive.

A generic name is usually given to a group of cancers, depending on the type of cells of their origin such as carcinoma (arising from the epithelial cells), which are further divided into squamous cell carcinoma, basal cell carcinoma and adenocarcinoma, sarcoma (arising from the mesenchymal cells), myeloma (arising from the plasma cells), leukaemia (arising from the white blood cells), lymphoma (arising from the lymphoid cells) and glioma (arising from the glial cells). Similarly there are other types of cancer depending upon the type of cells of their origin.

Conventional approach to manage cancer is: cut it (surgery), burn it (radiotherapy) and poison it (chemotherapy). Other techniques like bone marrow transplant, stem cell transplant, hormonal therapy, stereotactic radio surgery, cyber knife, gamma knife, cryosurgery, immunotherapy, photodynamic therapy and targeted chemotherapy have their own limitations. While undergoing conventional treatment such as chemotherapy, radiotherapy, hormone therapy, etc., some of the cancer cells may acquire an extra mutation and become resistant or refractory to the therapy, leading to progression or recurrence of cancer.

As cancer is a malady of genes & pathways so our research should be focused on finding new drugs, capable of repairing the damaged DNA, rectifying the chromosomal abnormalities and reversing the mutations in oncogenes, tumour suppressor genes & pathways. Such a wonder drug would cure cancer by normalising the cancer cells. To achieve this target, we have to concentrate on drugs having antimutagenic, antitumourangiogenic, proapoptotic and DNA repairing properties.

We also have to focus on immunoenhancing drugs, which are capable to boost immune system of the body against cancer by producing anticancer agents, known as cytokines (lymphokines and monokines), including interleukins, interferons, tumour necrosis factors and colony stimulating factors. The cytokines are capable to induce immunotherapeutic response within the body and eliminate the cancer cells without harming normal cells. In some cases spontaneous regression of tumour is observed as a result of immunotherapeutic response initiated by cytokines. Similarly, we have to find drugs, capable of boosting the activity of immune cells of the body such as T cells, NK cells, LAK cells and macrophages, which can destroy the cancer cells without harming the body.

Dr. S.P. Kaushal
Sino Vedic Cancer Clinic

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