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Biotechnology and Society---Part VI
Genetic
Diseases—Breast Cancer
The only way
to discover the limits of the possible is to go beyond them into the
impossible. -----Arthur C. Clarke (1917---)
Q: When is a disease not
really a disease but devastating all the same?
A: When it manifests in the form of undesirable growth.
Breast cancer: Cancer!
This very word will send shivers down one’s spine. It is the announcement of
the arrival of the angel (???) or agent of death. Cancer is not a disease in
the strictest sense of the word. It is just uncontrollable growth which
disables the cells from functioning normally. There are certain genes in the
body called oncogenes which can cause cancer under certain conditions. There
are also other genes called tumor suppressor genes which keep the oncogenes
under control. It is when oncogenes become active and tumor suppressor genes
go to sleep or become invalid that cancer occurs. The cells which proliferate
in a renegade fashion just “forget to die” when they should because the
tumor suppressor genes, which can teach the cancerous cell how to die, are out
of commission.
Among all cancers, breast and
ovarian cancers are the most prevalent and feared forms of cancer in women.
Family history is a big factor but spontaneous mutations caused by chemicals,
radiation, diet, and smoking in a given individual are also to blame. Every
woman is born with BRCA 1 (breast cancer gene 1) and BRCA 2 (breast cancer
gene 2) genes. These are the two tumor suppressor genes that, when functioning
normally, teach those cancer cells to commit suicide. In 1994 it was
discovered that women who carry mutations in BRCA 1 or BRCA 2 (in chromosome
17) are at higher risk of developing breast and ovarian cancer than those who
lack these mutations.
To test for BRCA 1 or BRCA 2,
a small blood sample is obtained and the DNA is analyzed for BRCA defects.
Currently there are over 2000 genetic mutations associated with these two
genes. Not all mutations carry the same risk for cancer; just those with the
mutations have a higher risk of developing cancer. Genetic testing for such
mutations is a controversial topic even among health care professionals since
there is no clear-cut correlation between the mutation and the incidence of
disease but only a linkage which is not understood very well. There are
recommendations for women who get tested positive for the mutations which
include daily exercise, and limiting alcohol consumption besides manual
examination and radiological screening when necessary.
Treatment: The
traditional treatment for breast and ovarian cancers has been and continues to
be chemotherapy---administration of drugs which are known to kill cancer
cells. This treatment is not very specific and the drugs kill cells other than
cancerous ones too. Several severe side effects such as nausea, and hair loss
are common. The most radical treatment employs radiation or surgery
accompanied by chemotherapy.
Genentech, an established
biotechnology company in San Francisco, did pioneering research in this field
studying several genes involved in the control and growth of cancer cells. It
was found that a gene called HER 2 (Human Epidermal growth factor Receptor 2)
plays a key role in regulating cell growth. When this gene is altered, extra
HER 2 receptors may be produced which would augment proliferation of cancer
cells (see figure below)
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Cancer cell growth and its
inhibition by antibodies: Source: http://www.gene.com/gene/products/information/oncology/herceptin/moa.jsp
In such cases the traditional
treatments may not be fruitful. Genentech decided to attack this receptor by
devising an antibody (immune agent) which would inhibit the function of HER 2
receptors. They named this antibody Herceptin®. These antibody molecules are
so specific that they target only the culprit HER 2 receptors. This drug was
approved by the US FDA in 1998 for use in breast cancer patients whose cancer
has metastasized (spread) beyond the breast and lymph nodes. Herceptin® has
been shown to slow the growth of cancerous tumors and in some cases the tumors
have completely disappeared. Presently, only those women who test positive to
HER 2 gene and whose breast cancer has spread are ideal candidates for this
type of treatment.
The success of Herceptin
suggests that the time for monoclonal antibodies (see definition below) in the
treatment of different cancers as well as other diseases has arrived. The
general structure of an antibody is shown below.
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Antibodies are natural
constituents of the body’s immune system and are very specific towards their
targets. They arrest unruly activities of the renegade cells and curb their
growth. Also they mop up disease-causing molecules, and microorganisms and
eliminate them from the body. In addition to breast cancer treatment,
monoclonal antibodies have been developed and are available for treatment of
colorectal cancer, Non-Hodgkin’s lymphoma, B-cell leukemia, and acute
myeloid leukemia. In addition to the use of monoclonal antibodies as such,
attempts are also made to couple other molecules to the antibody which would
be a “magic bullet” targeting the cancer cells and then killing them with
the help of the toxic molecules attached to the antibody. We shall discuss
monoclonal antibodies and their relatives in a separate article.
The final chapter has not been written
on cancer treatment yet. It would be an incomplete mission and a
dereliction of zeal on the part of cancer researchers if they could
not come up with a permanent cure. One can hope that gene therapy
could be perfected towards this end.
Definitions:
Antibody: A protein
produced by humans and higher animals in response to the presence of a
specific antigen.
Antigen: A substance
that, when introduced into the body, induces an immune response by a specific
antibody.
Clone: A cell or cell
product or organism genetically identical to the unit or individual from which
it was derived asexually.
Monoclonal antibody: A
highly specific, purified antibody that is derived from one clone of cells and
recognizes only one antigen.
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