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Strategies & Market Trends : Biotechnology Cancer Cures -- Ignore unavailable to you. Want to Upgrade?

To: Mike McFarland who wrote (131)	2/1/2000 12:58:00 AM
From: Neuroguy	Read Replies (1) \| Respond to of 226

Mike - here is the commentary on CLPA you requested. You asked how Aptosyn (exisulind), CLPA's cancer preventative drug works. In a nutshell, CLPA found that Aptosyn was binding a novel cGMP-specific phosphodiesterase enzyme (cGMP-PDE) expressed only in cancer and precancerous cells. It is known that cancers form by a failure to undergo apoptosis (programmed cell death). This can be induced by DNA damage, in case of radiation and chemos. Once the cell senses DNA damage, a biochemical cascade is initiated which ultimately results in the activation of caspase enzymes, which basically kill the cell. Unfortunately these treatments damage the DNA of all rapidly diving cells, hence the side effects like hair loss, etc (and death). But the caspase enzyme also needs to be phosphorylated, and a rise in cellular cGMP is required for this. Cancer cells seem to selectively express a novel form of cGMP-PDE which hydrolyses cGMP, thus denying the caspase this vital source. No cGMP, no hari kiri (apoptosis), and the cancer cell is immortal. Aptosyn blocks the enzyme, thus allowing caspase phosphorylation and apoptosis. The scheme is illustrated near the bottom of the CLPA technology page: cellpathways.com This page summarizes the technology in greater detail than I can/should here. Additional info on the company is summarized at: ragingbull.com The kicker is that normal cells do not express this enzyme, so the drug has little in the way of side effects. So you take a harmless drug, and whenever a cell tries to immortalize itself through the expression of the enzyme (= tumor development), the drug blocks the enzyme and kills the cell. Two PIII clinicacal trials have been completed, and FDA approval of their first NDA is currently awaited. Aptosyn was found to wash out polyps in an inherited form of colon cancer, FAP. It was also found to reduce the rate of rise of PSA on post-surgical prostate patients. An additional twist is that it enhances the therapeutic effect of chemos and chemopreventative like platinum compounds and cis-retinoic acid. RPR recently inked a deal to run combination trials with taxotere based on that data. Their second generation compound, CP461, has already passed safety trials and an announcement regarding which cancer indication they will study with it awaits. You can get further details from the company website (www.cellpathways.com) and the Raging Links of the RB CLPA board. That board is the best one to follow the stock. Hope this helps.