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Sausville Gives NCI Partners in Research Lecture

By Elisa Gladstone

Dr. Edward Sausville, associate director of NCI's Developmental Therapeutics Program, recently delivered the institute's Office of Management Partners in Research lecture. He described NCI's sophisticated approach to cancer drug discovery and development.

Dr. Edward Sausville, associate director of NCI's Developmental Therapeutics Program, describes NCI's sophisticated approach to cancer drug discovery and development.

Sausville explained that DTP is involved in all aspects of drug development, from the initial discovery in a basic research lab, to optimizing conditions and dosages for drug effectiveness in a clinic, to wide-scale testing in a large clinical trial. He contrasted the traditional empirical approach to drug screening that asks whether a new drug can reduce a tumor's size, to a new "rational" screening approach that asks which molecules are driving tumor growth. The lecture clearly detailed the merits of each approach to drug discovery, pointing out specific challenges faced by each type of screening.

"Empirical models are divorced from biology and lack the predictive power of in vivo testing," Sausville cautioned. "There is a poor correlation of nonhuman with human pharmacology."

According to Sausville, the rational screening approach also faces challenges. "Actual tumors are rarely driven by one gene or protein target, so different combinations of pathways need to be studied in an integrated way." He added that when designing drug studies, DTP distinguishes between cytotoxic and regulatory molecules as targets and uses models that realistically mimic integrated pathways in the cell.

Sausville informed the audience that DTP discovered or participated in the development of approximately one-half of the cytotoxic drugs currently used by oncologists for cancer chemotherapy. This achievement did not come easily, he reminded. Over the past 10 years, as many as 70,000 molecules have been studied in NCI's screening systems.

NCI actively solicits drugs from government laboratories, research institutes, academic institutions and companies throughout the world. DTP scientists systematically scan the latest literature for novel compounds and request samples of promising drugs. Another source of novel compounds comes from the Natural Products Branch, a part of DTP, which collaborates with agencies throughout the world to collect thousands of plant and marine organisms for screening in tumor cell lines.

DTP's drug screening enterprise has evolved into one that today combines both in vitro (cancer cells grown in a dish in a laboratory) with in vivo (animal) testing. The current system, which has been in place since 1990, is a combination of in vitro screening in human tumors, in vivo testing using hollow-fiber technique, and in vivo testing using xenografts.

Sausville concluded by highlighting DTP as a national resource with drug discoveries deposited in the public domain, offering the public access to drug development and clinical trials. As investigator- and science-driven rather than a profit-driven program, services are provided at no cost or on a cost-recovery basis.

For more information on DTP's drug discovery enterprise, visit http://dtp.nci.nih.gov.


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