General Information About Cancer

General Information About Cancer

What is Cancer?
Cancer is a group of many diseases caused by out-of-control multiplication and spread of abnormal cells.

Body cells normally follow an orderly growth division and destruction. Early in a person's life, normal cells divide more rapidly, 'till the person becomes an adult. Later normal cells in most tissues divide evenly to replace naturally lost cells or to repair injuries.

But cancer cells continue to multiply and can spread to other parts of the body.

 

Genesis Of a Cancer

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These cell collections form tumors and lumps that may press, invade and destroy adjoining normal tissue. Some cells from such a tumor can travel through blood stream, or the lymph system to other areas of the body. Here they may settle and form secondary tumors. This new focus is called metastasis. This still bears the name of the original part of the body where it started. Breast cancer spreading to the lungs is still called breast cancer metastasis.

Leukemia is a cancer of the blood and blood-forming organs (bone marrow, lymphatic system and spleen). There is no tumor as such. But these cancer cells circulate through other tissues where they accumulate.

Remember that all tumors are not cancerous. Benign (noncancerous) tumors do not metastasize and are not life threatening.

Cancer is named after the part of the body where it began, and by its appearance under a microscope. Different types of cancer vary in their rates of growth, patterns of spread and responses to different types of treatment. Hence treatment is aimed at the specific form of cancer.

The word cancer should not cause fear. Half of all men and one third of all women will develop cancer during their lifetime. Today, millions of people are living with cancer or are cured of the disease. The risk of developing many cancers can be reduced by changes in a person's life style, for example by stopping smoking or eating a better diet. The sooner a cancer is detected and the sooner treatment started, the better are a patient's chances of a cure.

Development of surgical techniques, anaesthesia, asepsis and advances in pathological tests and introduction of cancer cell killing drugs, and antibiotics against infecting organisms have changed the outlook and improved the prospects.

Virchow correlated microscopic pathology which allowed for a better understanding of the damage cancer does to a patient,& thus laid the foundation for the development of cancer surgery. Body tissues removed by surgery could now be examined and a precise diagnosis made. In addition, the pathologist could tell the surgeon whether the operation had completely removed all the tumor.

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What causes cancer?
A Brief History Of The Development Of Oncology

  • Egyptians blamed cancer on the Gods.
  • Hippocrates, the father of medicine, believed in the Humoral Theory of excesses or deficiences.
  • This was followed by the Lymph Theory - that cancer was composed of fermenting and degenerating lymph.
  • Blastema Theory . This proposes that cancer cells arose from budding elements (blastema) between normal tissue. The present view proposed by Rudolph Virchow (1821-1902) is that all cells including cancer cells, are derived from other cells.



Possible causes.

  • Chronic Irritation. Virchow proposed that chronic irritation was the cause of cancer.
  • German Surgeon Karl Thiersch proposed that cancers metastasize through the spread of malignant cells.
  • Even a Nobel Prize was wrongly awarded in 1926 for scientific research documenting stomach cancer being caused by a certain worm. Unable to confirm this research, the parasite theory is now given up.

Reflections on cancer occurrence.

  • An Italian doctor, Bernadrino Ramazzini, reported in 1713 the absence of cervical cancer and higher incidence of breast cancer in nuns and though this was related to their celibacy. This observation helped understanding the importance of hormonal factors such as pregnancy in modifying cancer risk.
  • Percivall Pott of Saint Bartholomew's Hospital, London described in 1775 an occupational cancer of the scrotum in chimney sweeps caused by soot collecting under their scrotum. This led to identification of a number of occupational carcinogenic exposures and public health measures to reduce cancer risk.
  • John Hill first recognized the dangers of tobacco in 1761 and published a book Cautions Against the Immoderate Use of Snuff

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Cancer and Surgery.
It was known for centuries that even after removal, cancer returns. It was considered that cancer was incurable.

Even though medicine progressed and flourished in some ancient civilizations, there was little progress in cancer treatment. The approach to cancer was Hippocratic (or Galenic) for the most part. To some extent this view that cancer cannot be cured has persisted . Even in the twentieth century patients are afraid of the disease, consider all cancers incurable and delay consulting a doctor until it is too late.

Treatments for cancer were only slowly developed. Some considered intervention might be more harmful than no treatment at all. Galen did write about surgical cures for breast cancer if the tumor could be completely removed at an early state. Surgery itself was very primitive with many complications, including blood loss. Only in the19th and 20th centuries, when major advances in surgery were made along with asepsis, antisepsis and anaesthesia, did cancer surgery improve.

After anesthesia became available in 1846, surgeons worked rapidly to advance the art and it became the century of the surgeon.

Bilroth in Germany, Handley in London and Halsted at Johns Hopkins performed cancer operations & attempted to remove all the tumor mass along with the lymph nodes in the region.

William Stewart Halsted at Johns Hopkins University, developed the radical mastectomy during the last decade of the 19th century. He and W. Sampson Handley, London believed that cancer spreads outward by invasion from the original growth and not so much through the bloodstream.

Stephen Paget, an English surgeon, concluded that cancer cells spread by way of the bloodstream to all organs of the body, but grew only in a few organs. In a brilliant leap of logic, he drew an analogy between cancer metastasis and seeds which are carried in all directions, but they can only live and grow if they fall on congenial soil. Paget's conclusion that cells from a primary tumor spread through the bloodstream, but were able to grow only in certain and not all organs was an accurate and highly sophisticated hypothesis that has been confirmed by the techniques of modern cellular and molecular biology almost a hundred years later. The understanding of metastasis is the key element in recognizing the limitations of cancer surgery. This lead to development of systemic treatments used after surgery to destroy cells that had spread throughout the body and to use less mutilating operations in treating many types of cancer.

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Cancer and Hormone Therapy.
Thomas Beatson from the University of Edinburgh in 1878 discovered that the breasts of rabbits stopped producing milk after he removed the ovaries and in 1896 he showed that one organ holds control over the secretion of another separate organ. The breast was held in control by the ovaries. He removed ovaries (oopherectomy) in advanced breast cancer and found that it often resulted in the improvement of the breast cancer patients. He also suspected that the ovaries may be the exciting cause of carcinoma of the breast. This work provided a foundation for the modern use of hormone therapy such as Tamoxifen for the treatment and prevention of breast cancer. Half a century after Beatson, a urologist from Chicago, Charles Huggins reported dramatic regression of metastatic prostate cancer following removal of testes. Later, drugs that blocked hormones were found to be effective treatment for prostate cancer. These are now under study to determine their possible use in prevention of prostate cancer.

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Cancer Treatment by Radiation.
In 1896 a German Physics Professor Wilhelm Conrad Roentgen described X-ray. 'X' is the symbol of an unknown quantity. Soon, systems were devised to use X-rays for diagnosis and in 3 years time, radiation was used in the treatment of cancer. In 1901, Roentgen received the first Nobel Prize awarded in Physics. Radiation therapy began with radium and with relatively low voltage diagnostic machines. It was discovered that daily doses of radiation over several weeks would greatly improve therapeutic response. The methods and the machines for giving radiation therapy have steadily improved to deliver radiation with great precision to destroy malignant tumor with minimal damage to neighbouring normal tissues.

At the same time, shortly after radiation was used for diagnosis and therapy, it was also discovered that radiation could cause cancer as well as cure it. Many radiologists at the beginning used to test the strength of radiation from their radiotherapy machine on the skin of their arms, looking for a dose to produce a pink reaction (erythema) that appeared like a sunburn. This was called erythema dose and was considered an estimate of the proper daily amount of radiation. This innocent self test by the radiologists produced leukaemia in many of them.

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Carcinogens: Substances that produce or promote cancers.
Other causes of cancer were slowly discovered. In 1911, Peyton Roux, at the Rockefeller Institute in New York described a sarcoma in chickens caused by Roux Sarcoma Virus. In 1915, cancer was induced in laboratory animals for the first time by applying a chemical, coal tar, to rabbit skin at Tokyo University. 150 years have passed after the most destructive source of chemical carcinogen known to man, tobacco, was first identified in London by John Hill. It was to be many more years that tobacco would be recognized again as a carcinogen.

Chemicals.
Today, we have learnt to avoid many specific substances that cause cancer. Coal tar and its derivatives, benzenes, some hydrocarbons, anilene (a substance used in preparing dyes) asbestos and many others. Radiation from a variety of sources including exposure to the sun is known to lead to cancer. To assure public safety occupational standards are prescribed for many substances like benzene asbestos, hydrocarbons in the air, pesticides, radiation etc.

Viruses.
Several viruses are now implicated in cancer. Long standing liver infection with hepatitis B virus can lead cancer of the liver.. A variety of Herpes virus, the Epstein Barr Virus causes infectious mononucleosis and has been implicated in Non Hodgkin's Lymphomas and nasopharyngeal cancer. The Human Immuno-deficiency Virus (HIV) is associated with increased risk of developing many cancers particularly Non Hodgkin's Lymphomas; Human Papilloma Viruses (HPV) are linked to cancers of the cervix, vulva and penis. These associations were recognized long before by scientists, before the mechanism by which they produced cancer was understood.

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Cancer and Chemotherapy.
During World War I, soldiers exposed to mustard gas had severe bone marrow depression. The first anti-cancer chemical was developed by the U.S. Army during the search for agents more effective than the mustard gas used in World War I. This was called Nitrogen Mustard. It proved to have remarkable effect against a cancer of lymph node called Lymphoma. Similar drugs (called Alkylating agents) killed rapidly proliferating cancer cells by damaging their DNA.

Two years later, Sydney Harber of Boston describe an antivitamin which blocked a critical chemical reaction necessary for DNA replication. This drug, aminopterine was followed by Methotrexate, commonly used in cancer treatment today. Now more drugs are discovered that block different phases in cell growth and replication. Thus the era of chemotherapy had begun. The first cure of metastatic cancer was obtained in 1956 when Methotrexate was given to treat a rare tumor called choriocarcinoma.

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Current status of research in cancer.
By the middle of the 20th century, we had instruments necessary to understand the complex problems of the chemistry and biology of cancer.

Watson and Crick discovered the exact chemical structure of DNA ,the basic material in genes.They received the Nobel Prize for their work. DNA contains the genetic code that gives orders to all human cells. After learning to translate this code, scientsts were able to see how genes work and how they may be damaged by mutations (changes or mistakes in genes). These modern techniques of chemistry and biology could solve many complex questions about cancer. Scientists already know that cancer could be caused by chemicals, radiation and viruses, and that sometimes cancer appeared to run in families. But with increasing understanding of DNA and genes, it now appears that it was the damage to DNA by chemicals and radiation, or introduction of new DNA sequences by viruses that often led to development of cancer. It has also become possible to pinpoint the exact site of the damage to specific genes in the DNA. Further discovery that sometimes defective genes are inherited and these genes are defective at the same points on which chemicals exerted their effect, was helpful. In other words, most carcinogens cause DNA damage (mutations), mutations lead to abnormal groups of cells (called clones), mutant clones evolved to ever more malignant clones over time and cancer progressed by further genetic damage and mutations.

Normal cells with damaged DNA die, cancer cells with damaged DNA do not. Recent discovery of this critical difference answers many scientific questions, not clear for many years.

Study of cancer biology is becoming a complex science as, slowly, medical scientists are identifying the genes that are damaged by chemicals or radiation and these genetic products, when inherited, can lead to cancer. The discovery of two genes that cause some breast cancers, BRCA1 and BRCA2, holds considerable promise because individuals with greater chances of developing breast cancers can now be identified.Other genes associated with some cancers that run in families have also been discovered such as cancers of colon, rectum, kidney, ovary, oesophagus, lymph nodes, skin melanoma and pancreas. Familial cancer is not nearly as common as spontaneous cancer, accounting for less than 15 percent of all cancers. But it is important to understand these cancers, because we can then identify persons at a higher risk with further research in genetics.

The approach to a patient has also become more scientific with clinical trials on a wide basis across the country. These clinical trials compare new treatments with standard treatments available and contribute to understanding the benefits and risks of treatment. Clinical trials also test theories about cancer learned in the basic science laboratories and ideas obtained from clinical observations on cancer patients. They contribute to the progress of science.

Early in the 20th century, the only curable cancers were the small localized tumors which could be completely removed by surgery. Later radiation was used after surgery to control the smaller tumor growths that were not removed by surgery. Finally, chemotherapy was added to destroy the tumor cells that had spread away from the site of surgery and radiotherapy. The use of chemotherapy or radiation therapy after surgery to eliminate the remaining malignant cells is called adjuvant therapy. Adjuvant therapy was successful first in breast cancer & is now used in other cancers like colon cancer, cancer of testes etc.

A major advance was recognition that multiple chemotherapeutic agents (combination chemotherapy) are more effective than single agents. This was particularly so in some types of very fast growing leukaemias and lymphomas; tumors of the cells of bone marrow and lymph nodes. More tumors are being cured today by appropriate combination therapy.

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Cancer treatment by biologic therapy.
Understanding of the biology of cancer cells led to the development of biological substances that mimic some of the natural signals the body uses to regulate growth. This cancer treatment, called biological response modifier (BRM) therapy, biologic therapy, biotherapy, or immunotherapy, is proving effective in several cancers as seen by the clinical trials.

Some of these biologic agents like Interferons, Interleukins, and other cytokines occur naturally in the body, and can now be produced in the laboratory. These agents are given to patients to imitate or influence the natural responses, either directly altering the cancer cell growth helping normal protective cells control the cancer. An exciting application of biologic therapy is identification of certain tumor targets called antigens and aiming an antibody at these targets. Originally, it was used to localize tumors in the body for diagnosis and now more recently has been used to attack cancer cells. One example is the use of the drug Rituximab, which is used in certain Lymphomas with significant improvement in survival as compared to conventional chemotherapy.

Cutting edge modifiers today include various agents which act by specifically targeting only cancer cells & not normal growing tissues, thus greatly reducing the side effects which are associated with conventional chemotherapy. Patients now have access to other novel agents as well, which attack & destroy the vascular supply to the cancer cells, thus leading to their death.

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Summary.
The growth in our knowledge of cancer biology, cancer treatment and prevention has been profound in recent years. We learned more about cancer in the last decade of the 20th century & in the first decade of the 21st than in all the previous centuries. This has been possible since all scientific knowledge is based on the previous knowledge acquired by hard work and discovery of our predecessors.

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