Angiogenesis Inhibitors

Traditional treatment of mesothelioma and other cancers has focused on resecting the tumor, radiating it or poisoning it. A relatively new approach, however, uses a seemingly obvious, but difficult method to attack the tumor starving it.

For a tumor to grow, it must develop its own internal network of blood vessels, peripheral to the blood vessels of the host body while still tapping into them. This new notion of starving the tumor hinges on preventing the tumor from developing new blood vessels by stopping vascular endothelial growth factor (VEGF), the process of spurring new blood vessel formation, thereby halting tumor growth and even potentially shrinking the tumor. Drugs that can accomplish this are called angiogenesis inhibitors or characterized as anti-VEGF.

Currently, there is one angiogenesis inhibitors available for treating mesothelioma.

SU5416, also known as semaxinib, is manufactured by pharmaceutical company Pharmacia's Sugen division. The drug is in a clinical trial for mesothelioma patients at the University of Chicago. Run by Dr. Hedy Kindler of the University of Chicago's Pritzker School of Medicine, the project is funded in part by the Mesothelioma Applied Research Foundation (MARF) a 501(c)(3) not-for-profit organization whose mission is to eradicate mesothelioma as a life-ending disease.

Other similar products are also in the pipeline. One such product is ZD 1839, more popularly known as Iressa. The product differs from angiogenesis inhibitors in that, instead of stopping vascular endothelial growth factor, it is a signal transduction inhibitor. The process of stopping the tumor is related to anti-VEGF drugs, but the method is different. The cancer cells have epidermal growth factor receptors (EGFRs). The receptors receive epidermal growth factors, and tyrosine kinase is released, causing the cancer cell to grow. Iressa attaches to the receptor instead and prevents the release of the tyrosine kinase, thereby stopping the cell growth.

It has gone through clinical trials with the Cancer and Leukemia Group B in Nevada, and more details about the trial may be found at the organization's website at http//www.calgb.org. Iressa is manufactured by pharmaceutical company AstraZeneca, which also has three other angiogenesis inhibitors in the pipeline. As of July 26, 2001, those three products were all expected to be in clinical trials by 2003 at the latest. As of January 3, 2002, AstraZeneca had submitted clinical data to the FDA seeking approval for the drug. It was granted fast track review and is expected to be on the market for treatment in mid-2002.

Other pharmaceutical companies are also producing angiogenesis inhibitors; however, they have yet to test these products for effectiveness against mesothelioma.

Genentech has developed Avastin (or bevacizumab); however, it is currently being tested primarily for breast and colorectal cancer as well as -- occasionally -- prostate cancer.

ImClone Systems, Inc. was developing an angiogenesis inhibitor called IMCC225, or cetuximab; they sold the licensing and research to BristolMyers Squibb, who renamed the drug erbitux and went on to send it to clinical trials. Presently, there are no trials of the drug open to mesothelioma patients.

Pfizer had developed a product called prinomastat; all clinical trials for the drug (none of which included mesothelioma) were halted in January 2001, due to disappointing responses in patients.

*** POSTED DECEMBER 21, 2001 ***