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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. |
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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.
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 work. 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'ss 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.
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.
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.
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.
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.
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.
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 giives 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 keow 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 recent 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. Familiar 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 l tumor cells that had spread away from the site of
surgery and radiotherapy. The use of chemotherapy 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.
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.
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 century 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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