Cell Pathways Presents Preclinical Research on Novel Anti-neoplastic Compounds

At the annual meeting of the American Association for Cancer Research, Cell Pathways Inc. (CPI), a Horsham, PA-based pharmaceutical company focused on cancer chemoprevention, reported several studies showing that selective apoptotic anti-neoplastic drugs (Saands) have potential for the prevention and treatment of cancer. In two separate studies, conducted in collaboration with scientists from the University of Illinois (Urbana-Champaign) and Columbia University (New York), these novel compounds were shown to induce apoptosis (programmed cell death) selectively in abnormal cells and inhibit the formation of premalignant lesions in breast and prostate cancer cells.

In the breast cancer study, the researchers demonstrated the ability of several of the compounds to inhibit the formation of chemically-induced premalignant lesions in a mouse mammary gland organ culture model. These included CP248, which, when compared to controls, inhibited the formation of precancerous lesions by greater than 80% at doses as low as 0.3 µM. CPI is currently conducting further preclinical development of CP248.

In the prostate cancer model, the researchers compared the effects of Exisulind and CP248 on human prostate cancer-cell lines, one androgen-sensitive (LNCaP) and one androgen-insensitive (PC3), with the effects of these compounds on cell cultures derived from normal human prostate (PrEC). Exisulind and CP248 induced apoptosis in both cancer cell lines in a time and dose-dependent manner. In contrast, neither Exisulind nor CP248 induced apoptosis in PrEC cells under conditions where both drugs had induced apoptosis in the cancer cells.

"This research suggests that SAANDs, which act by inhibiting a unique cyclic GMP phosphodiesterase (cGMP PDE), may eventually prove to be useful in the treatment of breast cancer and prostate cancer. In the case of prostate cancer, the preclinical data suggests that Saands may be helpful even in those cancers that have become resistant to current anti-androgen therapies," said Rifat Pamukcu, Cell Pathways' chief scientific officer and senior vice president of research and development.

Dr. Pamukcu continued, "Exisulind, the first Saand, is currently in clinical development for the treatment of precancerous colon polyps, including those formed by patients with adenomatous polyposis coli (APC), and the treatment of Barrett's esophagus and lung cancer, as well as for the prevention of recurrent prostate and breast cancers. We have also screened over 500 new active proprietary compounds for their ability to induce apoptosis via the inhibition of the novel cGMP PDE. Some of these, such as CP461 and CP248, show much greater potency than Exisulind in the preclinical apoptosis assays. CP461 commences Phase I studies this month."

For more information, contact Rifat Pamukcu, Cell Pathways Inc., 702 Electronic Drive, Horsham, PA 19044, 215-706-3800.