Targeted Therapy for Breast Cancer

Thought of by most as a silver bullet method for the treatment of breast cancer, the field of targeted cancer therapy is developing at a rapid rate, and may soon become the preferred treatment method for most cancers. The drugs used block the processes by which normal cells become cancerous and of tumor growth by interfering with specific molecular targets.

Targeted Therapy: What is it?

Similarly to chemotherapy, targeted therapy is a systemic treatment, which means that it can affect the entire body. Usually the drugs are injected into the bloodstream, but unlike chemotherapy drugs, which non-specifically attack any dividing cell, targeted drugs will only affect cells that express the specific target they are made to match. This means that the effect of targeted drugs on healthy cells is much less than that of chemotherapy.

Uses of Targeted Therapy

Targeted therapy drugs are designed in laboratories based upon known genes and proteins involved in various cancers. Cancerous cells express certain proteins differently than healthy cells. Scientists have been able to turn these proteins into molecular targets that can be sensed and locked onto by the drugs they build. Most of the targets are involved in one way or another with signaling cell growth and division. Consequently, most targeted drugs act to block the action of their targets, thus slowing or reversing tumor growth.

Targeted Therapy Drugs

There are several groups of targeted drugs either currently in use (approved by the FDA) or available through clinical research trials. These drugs fall into the categories of monoclonal antibodies, “small molecule” drugs, and apoptosis inducing drugs. Each category differs in the way in which it aims at its target.

Monoclonal Antibodies

Monoclonal antibodies are a family of drugs that recognize and fasten onto particular targets, like a key in a lock. They then cause cell death by stimulating either certain internal signals or an immune system reaction. Herceptin is a monoclonal antibody used in the treatment of breast cancer. It binds to a protein called HER-2, which can be over-expressed in some cancerous cells. By binding, it blocks growth factors that would lead to cell growth and division. Rituxan is an antibody used to treat several types of cancers by binding to CD20, a receptor protein, on the surface of immune cells called B-cells. This makes the cells susceptible to attack by the immune system, and may trigger a process of self-destruction called lysis in which the cell bursts.

Small-Molecule Drugs

“Small-molecule” drugs are also sometimes called signal transduction inhibitors because they interfere with abnormal proteins inside cancerous cells that are involved with cell growth and division. Some normal cells become cancerous because certain genes that stimulate cell division get turned on, or their off switch gets broken. Small molecule drugs target the protein products of these broken genes. Gleevec is a drug made to block an enzyme called tyrosine kinase that is necessary for stimulating cell growth. Alternatively, Iressa blocks a growth factor that would normally stimulate tyrosine kinase to promote cell growth. These drugs go after different small molecules in the chain of the signaling pathway that leads to cell growth.

Apoptosis

Apoptosis is a process otherwise known as programmed cell suicide. Normal cells will start the process of apoptosis when they sustain enough genetic damage to warrant it. Cancerous cells will continue to thrive even with significant amounts of damage to their DNA because the necessary internal controls are broken or blocked by other signals promoting cell survival. Apoptosis-inducing drugs act to cause cancer cells to commit suicide. A drug called Velcade works in this manner by blocking the actions of proteins called proteasomes, which are significant to the growth and survival of cells. Genasense blocks the activity of a protein called BCL-2, which promotes cell survival.

Side Effects of These Drugs

While these drugs produce fewer side effects than shotgun-type treatments like chemotherapy and radiation therapy, negative side effects should still be expected since no method is perfect and people may react differently. In fact, allergic reactions are common for people who do experience side effects during targeted cancer therapy. Doctors prefer to monitor patients receiving targeted therapy closely because most drugs available to patients are still in the clinical trial phase. Doctors are still learning how to use them safely and in combination with other drugs and how to identify the best patients for each new drug. With time and experience, targeted therapy is likely to become a preferred treatment method.

Kirsten Sanford is a science journalist & PhD candidate in the Molecular, Cellular and Integrative Physiology Graduate Group at the University of California, Davis. In addition to developing patient health education materials she also hosts a weekly science radio show (This Week in Science) dedicated to bringing current scientific news and research to the public.