Lesson F1 - Drugs, Chemicals & Cancer; Drugs used for the Treatment of Cancer Flashcards
In 1775, Percival Pott, a surgeon in London, England described cancer of the scrotum to
soot
In 1910, Clunet in France demonstrated that exposure of rats to x-rays caused cancer in rats.
This was followed in 1914 by the demonstration by other French workers that x-rays could
cause cancer in humans.
In 1915, two Japanese workers, Yamagiwa and Ichikawa produced cancer of the skin after
prolonged application of
coal tar to rabbit ears
In 1930, Kennaway and co-workers, who were skilful chemists, isolated highly carcinogenic
polycyclic hydrocarbons from
coal tar
Bladder cancer was described in 1895 by Rehm in aniline dye workers. 2-Naphthylamine was
used as a dye in the
dye industry. In 1938, Hueper showed that 2-naphthylamine caused cancer
of the bladder when administered to dogs. This led to prohibition of this dye in the dye industry.
Liver cancer was observed in the dead poultry and was traced to the peanut meal used as poultry
feed. The peanuts were found to be contaminated with a common fungus, Aspergillus flavus,
which produced
aflatoxin, a potent cancer-inducing agent in liver.
Smoking, mainly cigarettes, causes cancer of the
lung, upper respiratory tract, esophagus,
bladder and pancreas.
Saturated animal fat and red meat are strongly linked to cancer of the colon and of the rectum, as
well as to cancer of the
prostate. High intake of salt has been linked to stomach and other
cancers.
It has been shown that skimping on fresh vegetables and fruits can contribute to many different
types of cancer. It is thought that vegetables and fruit contain constituents that block
cancer inducing chemicals
DNA viruses are responsible for inducing some cancers. These viruses invade the living cells of
a host and utilize the host cells’ DNA- synthesizing and protein-synthesizing machinery to make
copies of themselves. Hepatitis B and Hepatitis C can cause
liver cancer
The human papilloma viruses, which are sexually transmitted, can cause cancer of the cervix.
The Epstein-Barr virus can cause a variety of cancers. Human immunodeficiency virus (HIV)
can cause
Kaposi’s sarcoma.
Helicobacter pylori, the bacterium responsible for causing stomach ulcers, has also been strongly
associated with
stomach cancer.
it is now clear that the carcinogens are in
general inactive as such but undergo metabolic activation by drug metabolising enzymes in the
body. The highly chemically reactive forms, termed the ultimate carcinogens, react irreversibly
with a DNA molecule, thus causing a change in the chemistry of the gene. This change is
perpetuated in subsequent divisions of the cell in which it occurs; in other words,
a mutation has
been induced. The genes affected may be oncogenes or tumor suppressor genes. Experimental
studies have shown that the cells must divide (cell proliferation) to make the genetic change
permanent.
There are three different categories of carcinogens –
– initiators, promoters and progressors
initiators. These agents damage
genes involved in control of cell division and facilitate the division and proliferation of cells.
Cancer arises when a single cell accumulates a number of mutations and escapes restraints on
cell division. The second category, promoters, do not damage genes but selectively enhance the
growth of cancer cells or precursors of cancer cells. Progessors allow the rapid growth of
tumors once they are established.
There are six categories of cancer treatment. These are
surgery, chemotherapy (use of drugs to kill cancer cells), radiation, biological therapies, hormone blocking and hormone-supplementing
therapies, and bone marrow transplantation.
The major goal of cancer chemotherapy is cure. Cure has, however, been achieved in only a
few cancers; for example, testicular cancer, Hodgkin’s disease and childhood leukemias. A second important goal is to prolong survival, while a third goal is the relief of symptoms. A
fourth goal is to provide psychological support to patients. A final goal is
ongoing clinical
research to provide improved chemotherapy for the future.
Benefit-risk assessment: The physician, in consultation with the patient, must weigh the
possible benefits of chemotherapy versus the
adverse effects of treatment in each clinical
situation
Mechanism of action: Drugs used in cancer chemotherapy act to
o kill tumour cells by inhibiting
protein synthesis, DNA synthesis, or cell division (mitosis).
A mutation is a change in the chemistry of the gene that is perpetuated in subsequent divisions
of the cell in which it occurs. In the mutant bacterium a mutation is manifested. A mutagenic
chemical is a chemical that promotes a
mutation by causing a change in the chemistry of the
gene
Adverse effects: Rapidly dividing normal cells in the body are also harmed by drugs employed
in cancer chemotherapy. Cells in the bone marrow which are the source of the red cells, white
cells and platelets in the blood are affected; as a result there will be a
decreased number of these
cells in the blood (cytopenia). The cells lining the gastrointestinal tract will be harmed resulting
in nausea, vomiting, and ulceration. Hair roots cells are harmed resulting in baldness.
Combination chemotherapy: Drugs are frequently used in combination. The rationale is that
cancer cells are less likely to defend themselves when attacked by a variety of drugs which attack
in
different ways
Alkylating agents:
An example is the nitrogen mustard, mechlorethamine, which
alkylates DNA, thereby damaging DNA.
Antimetabolites:
An example is the folic acid antagonist, methotrexate, which disrupts
cellular metabolism.
Natural products
An example is vincristine which is isolated from the Periwinkle plant;
it acts by arresting cell division. Another example is Paclitaxel (Taxol)
isolated from the Western Yew. It has been approved for use in ovarian
and breast cancer and acts by arresting cell division.
Antibiotics:
An example is doxorubicin which acts by damaging DNA.
Hormones:
An example is prednisone which suppresses cell division. Tamoxifen
suppresses the effect of the female hormone estrogen. It is used in
helping to prevent breast cancer in some women at high risk.
Biologicals:
A number of drugs derived through molecular biological techniques
inhibit cell replication by blocking cytokines, which normally control
cell growth. Some drugs are also antibodies to these cytokines.
Miscellaneous
An example is procarbazine which acts by damaging DNA.
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