Activities in this area are focused on the development of agents with novel mechanisms of action -- generally, agents that do not work through direct cytotoxic mechanisms. We have taken the approach of treating patients in a general phase I approach (a large variety of tumor types), or specifically treating prostate cancer patients. Prostate cancer has been chosen as a target because of it's resistance to standard cytotoxic approaches, suggesting the possibility that this disease may respond better to a non-cytotoxic type of agent. Agents and combinations that we have studied during the period of this report include: CAI Antimetastatic/anti-invasion agent; possibly antiangiogenic. Inhibits non-voltage gated Ca++ channels, and associated signalling. CAI-Taxol Mechanism of interaction is not clear. Studies being conducted in Lab of Pathology. CAI synergism does not hold for platinum compounds. Thallidomide Potent anti-angiogenic agent. Phase II ongoing in prostate cancer. Suramin Antiproliferative agent. Clinical potential still uncertain. (Phenylbutyrate& Inhibitor(s) of the mevalonate pathway. Produces secondary Phenylacetate& inhibition of oncoprotein isoprenylation, by depletion Antineoplastons) of farnysyl and geranylgeranyl. Lovastatin Inhibitor of the mevalonate pathway. Inhibits isoprenylation. Tamoxifen At high doses, inhibits PKC-mediated signalling. Flavoperidol Inhibits several tyrosine kinases, and associated signalling. UCN01 Inhibits selected PCK isoenzymes, and some cyclin- dependent kinases. Pentosan Agent that binds growth factors.
