AACR data indicate strong synergy of Hsp90 inhibitor, 17-AAG.

2004 MAY 6 - (NewsRx.com & NewsRx.net) -- Kosan Biosciences (KOSN) announced, at the American Association for Cancer Research, preclinical in vitro data on the cytotoxic and antiproliferative effects of Kosan's lead Hsp90 inhibitor, 17-AAG, when used in combination with 20 different standard and novel chemotherapeutics.

Data from the study demonstrated broad synergistic activity consistent with the mechanism of action of Hsp90 inhibition. Clinical investigation of several of these combinations in humans is ongoing.

The poster presentation, entitled "17-AAG (KOS-953), An Inhibitor of Hsp90 Function, Significantly Enhances the Cytotoxicity of Anticancer Drugs: An Effective Approach for Combination Therapy" (Abstract #1992), presented data demonstrating that 17-AAG, an analog of the polyketide geldanamycin, had synergistic effects with a broad range of anticancer agents in different tumor cell lines, suggesting that combining these agents with 17-AAG may enhance the effect of drug therapies by sensitizing tumor cells or potentiating their anticancer activity.

In the study, the antiproliferative effects of combining 17-AAG and over 20 different anticancer agents in the human colon cancer cell line DLD-1 and breast cancer cell line SKBr3 were evaluated. The anticancer agents represented a broad range of mechanisms including alkylating agents, antimetabolites, anticancer antibiotics, microtubule-interacting agents, and protein kinase inhibitors. The results showed that, in DLD-1 cells, approximately 80% of the drugs demonstrated synergistic effects with 17-AAG, whereas in SKBr3 cells, approximately 50% of the drugs showed synergistic effects. More than 25% of the drugs including microtubule-interacting agents docetaxel, vinblastine, vincristine, and KOS-862 were synergistic with 17-AAG in the colon and breast cancer cell lines regardless of treatment schedule.

According to Daniel V. Santi, MD, PhD, chairman and CEO at Kosan Biosciences, "The preclinical data suggests that by inhibiting multiple signal transduction pathways at one time, we can boost the efficacy of other chemotherapeutic regimens. Because ...