• 11/15/2007
  • San Francisco, CA
  • Rishi Sawhney, M.D.
  • insideBayArea.com

The introduction of “smart” laser targeted bombs and guided missiles with pinpoint accuracy have revolutionized modern warfare. A similar revolution is sweeping the world of cancer care. Targeted and smart anticancer drugs are increasingly being used in the treatment of a wide variety of cancers.

Thanks to the collaborative efforts of scientists, clinicians, the pharmaceutical industry and the government, more of these modern therapies are available in your oncologist’s office today.

Simplistically speaking, cancer results when a single cell continues to divide and produces more cells in an unregulated fashion. Understanding this basic fact led to the development of the first generation of anti-cancer drugs, which attack all actively dividing cells. These drugs known as cytotoxic chemotherapy have been the mainstay of most medical oncology practices. They are effective, but are also associated with toxicities of hair loss, mouth sores, nausea, vomiting and bone marrow suppression as they affect all actively dividing cells.

Increasing understanding of the biology and molecular profile of cancer cells has led to the realization that the regulation of certain cell surface molecules, genes and proteins is vital for the development of certain cancers. Through these changes, cancer cells are able to escape death, divide faster, spread to other parts of the body and can even recruit their own blood supply.

Identification of some of these cell surface receptors, genes and proteins has provided the basis for the development of drugs against such targets. These drugs seek out and kill cancer cells bearing that particular target and thus may have fewer side effects.
Examples of such targeted anti-cancer drugs include hormone-based therapies in breast and prostate cancer; antibody therapy for lymphomas, head and neck and breast and colon cancer; small-molecule inhibitors in lung, kidney and breast cancer; and other types of protein inhibitors.

Targeted antibodies have become the mainstay of cancer therapy for many cancers. They bind to cancer cells with high affinity and act by either directly killing the cell or by delivering radiation or cellular toxins that can be attached to them. These monoclonal antibodies range from partially to fully humanized antibodies, which have a lower risk of causing allergic reactions.

Currently, there are eight anti-cancer therapeutic antibodies approved by the FDA in the United States. These include Rituxan for non-Hodgkin’s lymphoma; Herceptin for breast cancer; Mylotarg for acute myelogenous leukemia; Campath for chronic lymphocytic leukemia; Zevalin and Bexxar for recurrent non-Hodgkin’s lymphoma; Erbitux for colorectal and head and neck cancer; and Avastin for colorectal and lung cancer.

Rituximab (Rituxan) was first approved in 1997. This antibody targets a cell surface receptor commonly found on many B-cell non-Hodgkin lymphomas. Trastuzumab (Herceptin) was approved in 1998 and is an antibody that targets an over-expressed receptor found in a certain subset of breast cancer patients. Bevacizumab (Avastin) is another antibody that was approved in 2004 for advanced stage colon cancer and now for certain patients with advanced lung cancer. These agents have shown efficacy and have also improved survival for many patients.

The other major class of targeted anticancer drugs includes small molecule inhibitors which are chemical compounds that bind to key proteins and enzymes required for cancer cell survival. These drugs are mostly in pill form and are taken orally. Among the notables one are Gleevec and Sprycel for chronic myelogenous leukemia (CML); Iressa and Tarceva for lung cancer; Sutent and Nexavar for kidney cancer and Tykerb for breast cancer.

Imatinib Mesylate (Gleevec) was approved in 2001 and is an inhibitor of a fusion protein responsible for the development of CML, which is a cancer of the blood and bone marrow. Sunitinib (Sutent) is an oral, multi-targeted receptor inhibitor approved in 2006 for the treatment of advanced kidney cancer. Sorafenib (Nexavar) is also an oral drug that targets multiple receptors and pathways and was approved in 2006 for the treatment of advanced kidney cancer.

Although these new drugs are more targeted, they do come with some side effects and are very expensive. Continued research will further revolutionize oncology drug discovery, as targets are identified. Also, employment of advanced molecular diagnostics will help medical oncologists tailor each therapy to a particular patient’s tumor profile. This will truly usher us into an era of practicing personalized medical care for each patient with cancer.

Dr. Rishi Sawhney is a medical oncologist with Valley Medical Oncology Consultants and is on staff at St. Rose Hospital, Eden Medical Center and San Leandro Hospital. His offices are in Hayward and Castro Valley.