Targeted Therapy: Monoclonal Antibodies, Anti-angiogenesis, and Other Cancer Therapies
Targeted therapy is the result of about 100 years of research dedicated to understanding
the differences between cancer cells and normal cells. To date, cancer treatment
has focused primarily on killing rapidly dividing cells because one feature of cancer
cells is that they divide rapidly. Unfortunately, some of our normal
cells divide rapidly too, causing multiple side effects.
Targeted therapy is about identifying other features of cancer cells. Scientists
look for specific differences in the cancer cells and the normal cells. This
information is used to create a targeted therapy to attack the cancer cells without
damaging the normal cells, thus leading to fewer side effects. Each type of
targeted therapy works a little bit differently but all interfere with the ability
of the cancer cell to grow, divide, repair and/or communicate with other cells.
Modern targeted therapy types include the use of monoclonal antibodies and anti-angiogenesis
drugs, both of which are described in greater depth here.
The different types of targeted therapies are defined in three broad categories.
Some targeted therapies focus on the internal components and function of the cancer
cell. The targeted therapies use small molecules that can get into the cell
and disrupt the function of the cells, causing them to die. There are several
types of targeted therapy that focus on the inner parts of the cells.
Other targeted therapies target receptors that are on the outside of the cell.
Therapies that target receptors are also known as monoclonal antibodies. Anti-angiogenesis
drugs target the blood vessels that supply oxygen to the cells, ultimately causing
the cells to starve.
Researchers agree that targeted therapies are not a replacement for traditional
therapies. Targeted therapies involve production of components such as monoclonal
antibodies or anti-angiogenesis drugs may best be used in the short term, combination
with traditional therapies. More research is needed to identify which cancers
may be best treated with targeted therapies such as monoclonal antibodies or anti-angiogenesis drugs and
to identify additional targets for more types of cancer.
Targeted Cancer Therapies
- Signal Transduction inhibitors: Imatinib Mesylate (protein-tyrosine kinase
inhibitor), Genefitinib (epidermal growth factor receptor tyrosine kinase inhibitor
- EGFR-TK), Cetuximab (epidermal growth factor receptor), Lapatinib (epidermal
growth factor receptor (EGFR) and human epidermal receptor type 2 (HER2) tyrosine
- Biologic Response Modifier Agent: Denileukin Diftitox
- Proteasome inhibitor: Bortezomib
Using Monoclonal Antibodies as Targeted Therapy
Monoclonal antibodies are a relatively new type of "targeted" cancer therapy.
Antibodies are part of the immune system. Normally, the body creates antibodies
in response to an antigen (such as a protein in a germ) entering the body.
The antibodies attach to the antigen in order to mark the antigen for destruction
by the body's immune system. In the laboratory, scientists analyze specific
antigens on the surface of cancer cells (target) to determine a protein to match
the antigen. Then, using protein from animals and humans, scientists work
to create a special antibody that will attach to the target antigen. An antibody
will attach to a matching antigen like a key fits a lock. This technology
allows treatment to target specific cells, causing less toxicity to healthy cells.
Monoclonal antibody therapy can be done only for cancers in which antigens (and
the respective antibodies) have been identified. The following are monoclonal
- Gemtuzumab ozogamicin
- Ibritumomab Tioxetan
Anti-angiogenesis (Angiogenesis Inhibitors)
Anti-angiogenesis is the process of stopping the formation of new blood vessels.
A little background on angiogenesis would be helpful to understand how this
In normal tissue, new blood vessels are formed during tissue growth and repair (i.e.
a healing wound), and during the development of baby during pregnancy. Blood
vessels carry oxygen and nutrients to tissue that are necessary for growth and survival.
In cancer, tumors need blood vessels in order to grow and spread. Through
a complex process, endothelial cells (which line the blood vessels) are able to
divide and grow and create new blood vessels. This process is called angiogenesis
and it occurs in both healthy tissue and in cancerous tissue.
There are known substances that both stimulate angiogenesis and stop, or inhibit,
angiogenesis. Since 1971, Judah Folkman, a surgeon from Massachusetts, has
been researching these substances. His theory is that if the development of
new blood vessels could be stopped, a tumor could not grow or spread. The
cancer would eventually starve to death. Since that time, scientists have
been studying the production of both natural and synthetic (man made) substances,
called anti-angiogenesis agents or angiogenesis inhibitors. In animal studies,
these angiogenesis inhibitors have successfully stopped the formation of new blood
vessels, causing cancer to shrink and die.
It is too early to know if these angiogenesis inhibitors will be effective components in
human cancer therapy. Currently, there are more than 20 compounds being tested
on a variety of cancers in clinical trials. Some of these angiogenesis inhibitors
are available commercially, approved by the FDA for other uses. Drugs like
Interferon-alpha and Thalidomide are believed to have some ability to inhibit angiogenesis
and are being studied in specific cancer types of cancers. Other anti-angiogenesis drugs
are new, not approved by the FDA and can only be given in clinical trial situations;
most often for advanced disease. Researchers are working to learn the safety
and efficacy of these medications.
The hope is that angiogenesis inhibitors will have less toxicity, since it would
only affect the development of new blood vessels. However, since these medications
are given systemically (absorbed by the whole body), unexpected side effects are
likely. It is also too early to tell if anti-angiogenesis drugs will damage
healthy blood vessels that may be needed elsewhere in the body. The benefits
and risks of anti-angiogenesis drugs will be determined through clinical trials
over the next several years.
Using (and enhancing) the body's natural systems and processes to aid in cancer
therapy is closely related to the topic of immunotherapy and the immune system in
More Chemotherapy Information:
Protocols - How Chemotherapy Works
How Chemotherapy Is Given
How Doctors Decide Which Chemotherapy Drugs To Give
How Long Chemotherapy Is Given
How To Tell If Chemotherapy Is Working
Cancer Cells & Chemotherapy
Short & Long Term Side Effects of Chemotherapy
Cancer Clinical Trials