Discovery of a Small Molecule in the Treatment Development of Pancreatic Cancer

Abstract

KRas gene is the most essential oncogene in human cancer, and the oncogenic mutations are found in approximately 90% of patients with pancreatic cancer. However, effective therapies for these patients are unavailable currently. In general, multiple cellular processes are affected by the oncogenic Ras mutants via exploiting their extensive signaling, in which the Ras-MAPK signaling cascade exerts important roles. Thus, targeted-Ras therapies are beneficial for the treatment of pancreatic cancer. Using an innovative SPA (Specificity and Affinity) drug screening strategy (which searches for potential lead compounds reaching the maximization of the performances on the binding affinity and binding specificity predictions), which begun four years ago, the CIAC researchers have identified a core of 26 small-molecule agents targeted KRas oncoprotein from NCI/DTP Open Chemical Repository [2]. From these agents, the researchers were interested in focusing on APY606 since the fact was uncovered that in pancreatic cancer, its anti-cancer property is the most promissing, explained Dr. Zuojia Liu, a researcher at CIAC. In the studies, the researchers assessed the effect of APY606 on antitumor activity against human pancreatic cancer cell lines, Capan-1 and SW1990, and on the Ras-MAPK and apoptosisrelated signaling cascades. The combined data suggest that APY606 exerts extensive antitumor activities for the therapeutic intervention in