Ras family signaling: therapeutic targeting (original) (raw)

Mutationally activated and oncogenic versions of the ras genes were first identified in human tumors in 1982. This discovery prompted great interest in the development of anti-Ras strategies as novel, target-based approaches for cancer treatment. The three human ras genes represent the most frequently mutated oncogenes in human cancers. Consequently, a considerable research effort has been made to define the function of Ras in normal and neoplastic cells and to target Ras for cancer treatment. Among the anti-Ras strategies that are under evaluation in the clinic are pharmacologic inhibitors designed to prevent: (1) association with the plasma membrane (farnesyltransferase inhibitors), (2) downstream signaling (Raf and MEK protein kinase inhibitors), (3) autocrine growth factor signaling (EGF receptor inhibitors), or (4) gene expression (H-ras and c-raf-1). Although a number of these inhibitors have demonstrated potent anti-tumor activities in preclinical models, phase l-lll clinical...