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 kinase inhibitor.
• Biologic Response Modifier Agent:  Denileukin Diftitox
• Proteasome inhibitor:  Bortezomib

Monoclonal Antibodies

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 antibodies:

• Alemtuzumab
• Gemtuzumab ozogamicin
• Rituximab
• Trastuzumab
• 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 works.

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 general.

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