Ha-ras Oncogene and Anticancer Drug Resistance

Extensive research on the Ras proteins and their functions in cell physiology over the past 30 years has led to copious approaches that reported the possible role of Ras not only in tumorigenesis but also in many developmental disorders. One of the hallmarks of human cancers is the intrinsic resistance to apoptosis. In this review we focus on anticancer drug sensitivities towards Ha-ras oncogene overexpression in vitro, reveal the downstream Ras effector molecules involved in the signaling pathways and the effect on cell cycle progression. Furthermore, we particularly emphasized 5-fluorouracil, Lovastatin, Tumor necrosis factor-α and Xanthone in selective suppression of Ha-ras-related tumorigenesis. Hence, a better understanding of the molecular mechanisms underlying tumor sensitivity to apoptotic cell death is anticipated to provide the basis for a rational approach to develop molecular targeted therapies.