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Surgery
Surgery is the oldest and still considered the most
effective therapeutic choice for solid tumors. By 1600
B.C, Egyptian physicians were excising tumors using
knives. In the second century AD, Galen theorized that
cancer is a systemic disease caused by an excess of
black bile and therefore not amenable to cure by surgical
resection. His teachings held sway for 1600 years. Then
in 18 century, Valsava hypothesized that cancer is at
first a local disease curable by operation, that it
spreads via the lymphatic systems. In 19th century,
Billroth performed the first modern cancer operation,
mastectomy. Halsted from Johns Hopkins University developed
the modern surgical principle of oncology, i.e., "en
bloc" resection of primary tumor and lymph nodes.
Halsted is considered to be the father of modern surgical
oncology.
Today, surgery is indicated for about 70% cancers and
it remains the one of the most effective therapeutic
modalities. Advances in surgery include a move toward
less radical operations. Radical or curative surgery
removes the cancer, adjacent tissues, and nearby organs
or lymph nodes that might have been invaded by cancer
cells. Palliative surgery treats the complications of
cancer to help relieve discomforts. In addition to providing
local or regional treatment of the cancer, information
gained during surgery is useful in determining the likelihood
of cancer recurrence and whether chemotherapy or radiation
will be necessary.
During the past decades, basic changes have occurred
in our understanding of cancer biology. Now most cancers
are viewed as "systemic" disease from their
inception, or at least from the moment they are detectable.
Modern techniques reveal micrometastasis in blood or
bone marrow even in patients who are classified as "stage
I". It is the micrometastasis that eventually leads
to clinical recurrence. Thus, any local therapy, surgery
or radiation or both, can not hope to affect systemic
micrometastasis and have a significant impact on patients
outcome. Only systemic therapy can provide further advances
in cancer treatment.
With this new understanding, the past 2 or 3 decades
have witnessed the emerging of "multidisciplinary"
concepts; different therapeutic modalities are applied
to treatment of individual patients.
Radiation Therapy
The clinical applications of radiation therapy or radiotherapy
were initiated shortly after the discovery of natural
radioactivity by Marie Curie and X-ray by Roentgen.
This modality relies on regional destruction of tumor
tissue (and surrounding normal tissue) through ionizing
radiation that disrupts the cellular DNA.
Radiation therapy may be externally or internally originated.
External radiation delivers high-energy rays directly
to the tumor site from a machine outside the body. Brachytherapy,
or interstitial radiation, a form of internal radiation,
involves the implantation of a small amount of radioactive
material in or near the cancer.
In today's practice, radiation is used to cure or control
cancer. It is applicable for about 60% of all cancers.
Radiation therapy is not without side effects. Marie
Curie, the founder of radiation therapy, died of leukemia
at a young age from unprotected use of radioactive materials.
Modern radiation therapy, aided by precise localization
of tumor with computer technology, has much less side
effects.
Like surgery, radiation therapy is a local treatment
modality, hence is not typically useful in eradicating
cancer cells that have already spread to other parts
of the body.
Chemotherapy
 Chemotherapy
involves the use of chemical compounds to kill cancer
cells. Although use of herbs and heavy metals or poisons
to treat cancer dated back thousands of years in traditional
Chinese medicine, the modern chemotherapy is started
at Yale University after World War II. Yale researchers
noted that mustard gas, a chemical warfare, could heavily
damage mice bone marrow and lymphatic tissue. This observation
led to the successful administration of mustard in patients
with lymphomas at Yale-New Haven Hospital in 1943.
Chemotherapy is one of the main cancer treatment modalities.
Today, it is given to about 70% to 80% of American cancer
patients, with a cure rate of 92% for testicular cancers,
40-80% for lymphomas, and significantly improves outcome
for breast cancer, colon cancer, and recently lung cancer
and prostate cancer.
Chemotherapy is considered a systemic treatment. Chemotherapy
is different from local therapies like surgery or radiation
in that the cytotoxic drugs circulate in the blood to
the organs where the cancer may have spread and can
eradicate cancer cells at sites great distances from
the original tumor.
The potent drugs used in chemotherapy destroy constantly
dividing cancer cells, but unfortunately, they also
kill healthy growing cells, causing many side effects.
The most common side effects are nausea, vomiting, mouth
ulcers, hair loss, and weakened immune system. However,
many side effects once associated with chemotherapy
are now efficiently managed, allowing most patients
on chemotherapy to work and and participate in normal
activities while receiving treatment.
In the recent years, progress on chemotherapy development
plateaued. With new understanding of cancer biology,
more "targeted "therapies have been introduced
into clinical practice, with the promise of less toxicity
and more effectiveness.
Targeted Therapies
Targeted therapies-treatments that zero in on cancerous
cells and spare normal cells, offer the potential of
a new generation of drugs to kill cancer cells with
pinpoint accuracy. With the precise targeting, it kills
only the cancer cells and minimizes damage to normal
cells. Advances in biotechnology have led to the successful
development of various types of targeted therapies.
Monoclonal Antibodies
The latest development in targeted therapies is monoclonal
antibodies. Monoclonal antibodies are proteins that
our body normally makes to fight infections or other
foreign attacks. Cancer investigators attempted to make
specific antibodies against certain targets on malignant
cells. So the concept was that if you could take an
antibody, target it directly to the cancer cell, you
could then cause the cancer cell to die. This has led
to a host of new treatments for malignancies. Because
they specifically fight cancer cell, monoclonal antibodies
are called targeted therapies. And the list of those
available as treatment options in cancer, is growing
very rapidly.
The first monoclonal antibody was Rituximab, or Rituxan,
in the treatment of lymphoma. That was followed quickly
by a drug called Herceptin, which is used in the treatment
of breast cancer.
For cancer patients today, the ongoing research into
targeted therapies like monoclonal antibodies means
a whole new world of treatment possibilities which carries
minimal toxicities.
Antiangiogenesis
The newest weapon in the war on cancer is called antiangiogenesis.
Tumor cells require oxygen and nutrients to grow, reproduce,
and survive. Angiogenesis, the development of new oxygen-carrying
blood vessels, allows the tumor not only to increase
in size, but also to spread to other sites in the body.
Anti-angiogenic drugs, the inhibitors that block the
creation of new blood vessels to prevent tumor growth
and spread are currently under vigorous investigation
the first of such drugs, Avastin, was approved by FDA
to treat colon cancers. Avastin has proven to be one
of the most effective therapies for colon cancers, and
most likely works well for other malignancies too.
Tyrosine kinase inhibitors
Scientists have known for years that many cases of cancer
are driven by a flaw in the complex cell communication
system, the so-called signal transduction pathways.
A healthy cell, with the right number of growth factor
receptors (i.e., EGFR) on the outside, divides normally
in response to the body's needs. Cancer cells have too
many receptors. They respond to the growth factor signal
by dividing too quickly. Therefore, blocking the signal
transduction should stop the uncontrolled growth of
cancer cells. The drug Gleevec® (imitinib mesylate)
is the first one of this type of targeted therapy that
FDA approved for myeloid leukemia. It inhibits a mutated
form of tyrosine kinase and stops the abundant growth
of cancerous white blood cells in chronic myeloid leukemia.
Erbitux blocks EGFR and it was approved by FDA for colon
cancer.
Immunotherapy and the Vaccines
In 1890, Dr. Coley, a brilliant surgical oncologist
at Memorial Sloan-Kettering Cancer Hospital in New York,
found that most of his patients who survived after surgery
had developed an infection shortly after the surgery.
He then injected a cocktail of bacteria, known as Coley's
toxins, into his cancer patients with notable cure rates.
Dr Coley's clinical experimentation opened a new era
in cancer therapy- immunotherapy.
Probably the most promising form of cancer treatment
is in immunotherapy, where scientists are developing
several experimental cancer vaccines that could lead
to the eradication of cancer in the near future, like
we did for polio or smallpox decades ago. Most cancer
cells can escape or hide from the immune system, some
times making the immune system weaker, which is why
people relapse even years after treatment. The vaccine,
which contains tumor cells or antigens, stimulates the
patient's own immune system, which produces special
cells that kill cancer cells and prevent relapses of
the cancer.
Recently scientists discovered a special cell type called
dendritic cells. It contains many projections, like
antenna, hence the name dendritic cells. Dendritic cells
break the antigens on the cancer cell surfaces into
smaller pieces. The dendritic cells then display those
antigen pieces, acting as "most-wanted posters"
for the immune system, so the cancer cells can not hide
from the immune system anymore. Once the immune system
finds and recognizes the cancers cells, it produces
special cells, like T cells, that kill cancer cells
and prevent relapses of the cancer. Dendritic cells
can greatly enhance the effectiveness of cancer vaccine.
While scientists have had some success with cancer vaccines,
it is still much too early to predict when a true cancer
vaccine will be developed. However, science has brought
us closer than ever to being able to develop a method
that could eradicate some forms of cancer in our lifetime,
if not all cancer entirely.
12/11/2005
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Surgery,
chemotherapy and radiation are the main tools used to
treat cancers today. The kind of cancer treatment varies
depending upon the type and stage of cancer and the
general health condition of the patient. The aim of
conventional therapy is to eliminate cancer cells.
