Research

The laboratory is studying the effects of new generation antifolate inhibitors of de novo purine synthesis on energy metabolism in human prostate cancer cells. It has been shown that the single most frequently disrupted group of genes found in these cancer cells are those that function in purine biosynthetic pathways thus our interest in studying the near and long term effects of drugs that impair the de novo pathway. Results to date indicate that in the presence of such drugs and in addition to a overall rapid depletion of ATP, a complex array of alterations in several different signaling pathways including AMPK, AKT and p53, occur and that reliance upon salvage pathways to support purine synthesis as a consequence of inhibition of de novo synthesis lead to long term growth arrest, and to the on set of senescence. Studies focused upon the manner in which these various signaling pathways interact as well the on the mechanisms responsible for acquisition of resistance to these drugs are in progress.