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New horizons, treatments in anticancer chemistry

Many employ compounds derived from natural products

SAN FRANCISCO, March 27 -- With the help of chemistry, researchers are continuing their quest to keep cancer in check. A futuristic vaccine and several unique approaches to inhibiting cancer growth are underway. Many new compounds, including epothilones and bryostatins, are derived from natural products. A special symposium on the topic will take place at the 219th national meeting of the American Chemical Society, the world's largest scientific society, in San Francisco, Calif., March 26-30. Selected studies are described below.

• Squeezing hope from a marine organism: Bryostatin, a promising new anticancer agent derived from moss-like aquatic organisms called bryozoans, appears to prevent tumor-promoting compounds from binding to designated receptor proteins. Bryostatin is in advanced human clinical trials, both as a single agent and in combination therapies. (George R. Pettit, Ph.D., Cancer Research Institute, Arizona State University, Tempe, Ariz.; ORGN 242, Monday, March 27, 9:20 a.m., Moscone Convention Center, Room 103, Exhibit Level. See page 140 in the final program.)

• Advances in vaccine development: Designed to force the immune system to recognize tumor-specific antigens and produce antibodies that destroy them, vaccines could be used to keep tumors from recurring after conventional treatment. Targeted areas include prostate, breast, ovarian and colon cancer. Researchers will report on the latest advances, including some vaccines now in clinical trials. (Samuel J. Danishefsky, Ph.D., Sloan-Kettering Institute for Cancer Research and Columbia University, New York, N.Y; ORGN 244, Monday, March 27, 10:40 a.m., Moscone Convention Center, Room 103, Exhibit Level. See page 140 in the final program.)

• Promising bacterial compounds:A new class of anticancer drugs called epothilones, derived from common soil bacteria, attacks drug-resistant tumors. Although these agents appear to be much more potent than similar microtubule-stabilizing drugs, they carry a high risk of toxicity. Researchers are taking a variety of approaches to creating analogs that are safer than the natural drug. The first human trial of this experimental class of drug analogs started recently. (Gregory Vite, Ph.D., Bristol-Myers Squibb, Princeton, N.J.; ORGN 286, Monday, March 27, 1:30 p.m., Moscone Convention Center, Room 102, Exhibit Level. See page 141 in the final program.)

• First oral medication with Taxol®-like activity: A new anticancer agent is poised to become the first orally active medication with a mechanism similar to Taxol®, which stops tumor growth by stabilizing the tiny strands (microtubules) that separate the chromosomes during cell division. Taxol® and other microtubule-stabilizing agents are currently administered by injection or intravenously. The new agent, which appears to be especially promising for the treatment of breast and colon cancer, attacks tumors that are resistant to Taxol® and may have fewer side effects. Known as IDN5109, it is in clinical trials. (Iwao Ojima, Ph.D., State University of New York at Stony Brook, N.Y.; ORGN 245, Monday, March 27, 11:20 a.m., Moscone Convention Center, Room 103, Exhibit Level. See page 140 in the final program.)

• New anticancer agents from algae: Cryptophycins are derived from blue-green algae. Unlike Taxol® and epithilones, which inactivate microtubules by stabilizing their structure after they form, cryptophycins inhibit tumor growth by preventing the formation of microtubules. A synthetic cryptophycin analog is in Phase I clinical trials. (Chuan Shih, Ph.D., Lilly Research Laboratories, Indianapolis, Ind.; ORGN 291, Monday, March 27, 4:40 p.m., Moscone Convention Center, Room 102, Exhibit Level. See page 141 in the final program.)

• New approach to blocking tumor formation: The enzyme farnesyl protein transferase (FTPase) processes an important chemical involved in tumor formation. Researchers have developed compounds that block FTPase, resulting in decreased tumor formation in preclinical models. Some of these compounds, which are expected to have few side effects, are currently undergoing human clinical trials. (J.B. Gibbs, Ph.D., Merck Research Laboratories, West Point, Penn., MEDI 292, Tuesday, March 28, 8:30 a.m.; Arthur G. Taveras, Schering-Plough Research Institute, Kenilworth, N.J, MEDI 293, Tuesday, March 28, 9:10 a.m.; J.T. Hunt, Bristol-Myers Squibb, Princeton, N.J, MEDI 294, Tuesday, March 28, 9:50 a.m. All presentations in the Moscone Convention Center, Rooms 130/131. See page 134 in the final program.)

• Stopping runaway blood vessel growth: Angiogenesis is the development of new blood vessels. In cancer, this process becomes unregulated, leading to uncontrolled tumor growth and spread. Researchers have designed a synthetic compound that stops tumor cell growth by interfering with angiogenesis. The new compound is in preclinical studies. (Peter G. Ruminski, Ph.D., Searle Research and Development, Monsanto Company, North Chesterfield, Mo., MEDI 295, Tuesday, March 28, 10:30 a.m., Moscone Convention Center, Rooms 130/131. See page 134 in the final program.)

A nonprofit organization with a membership of 161,000 chemists and chemical engineers, the American Chemical Society www.acs.org publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

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