Cell Pathways CP461 demonstrates multiple anti-cancer ...( ty in Lung Cancer In a study comp...)

In a study comparing the activity of CP461 alone with that of docetaxel in rats implanted with human A459 non-small cell lung cells, groups of 12 animals each received either 10, 25, 50 or 100mg/kg daily of oral CP461 for 10 weeks, 2.5 mg/kg of once-weekly intravenous docetaxel for six consecutive weeks, or placebo. Mean survival times for rats receiving CP461 monotherapy at 25-100 mg/kg doses were statistically significant (p < 0.02, 0.002 and 0.005, respectively) compared to control rats. Also, mean survival times in rats receiving docetaxel were significantly greater than the control rats (p = 0.05). There was no statistical difference in rats receiving CP461 versus docetaxel therapy. Moreover, in addition to higher apoptosis indices, the CP461-treated rats had dose-dependent reductions in proliferation rates as measured by immunohistochemical studies of the NSCLC tumors.

Cell Pathways researchers also investigated the mechanisms by which CP461 achieved its anti-cancer effects in the cells used for lung tumor formation, A459 cells. PDE5 and PDE1, the molecular targets of CP461, were higher in lung tissue containing A459 NSCLC cells compared to normal bronchial epithelial and alveolar cells. The researchers also found that CP461 treatment increased both the number of apoptotic cells and the percentage of cells blocked at the G2/M stage of the cell cycle (thus preventing cell division).

This is the first demonstration of the anti-proliferative effect of CP461 combined with selective apoptotic activity in an animal model of lung cancer, said Dr. Pamukcu. These results suggest a strong rationale for the clinical investigation of CP461 as a single-agent in cancer.

CP461 Disrupts Ability of Cells to Divide

Previous research has shown that CP461 and other SAANDs induce apoptosis in cancer cells. A separate presentation on CP461 provides insight on the mechanism by which the drug achieves its additional ant
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Contact: Joan Kureczka
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8-Apr-2002