From Ras signalling to ChoK inhibitors: a further advance in anticancer drug design

Abstract 

Cancer is a genetic disease, most prominent in developed countries, with still a high mortality rate [1]. Cancer cells are continuously proliferating, and this uncontrolled growth is mediated by the activation of different signal transduction pathways that ultimately lead to the carcinogenic process. Consequently, a large effort has been devoted to design specific molecules that interfere with these signaling cascades involved in tumorigenesis. In the last decades, research has resulted in improvements in both detection and treatment of cancer. However, it is still necessary to develop novel antitumoral therapies that would allow an appropriate treatment for each cancer patient. These novel, tumor- and patient-specific therapies will have a dramatic impact in improving the overall survival rates. Ras is one of the most important oncogenes so far identified in human carcinogenesis. Understanding the regulation of Ras-dependent signalling under normal and oncogenic environments may provide clues for the design of efficient specific antitumor strategies. In this review we will illustrate how the family of Ras GTPases may be a valid model for the development of new cancer therapies.

Keywords: Carcinogenesis, Signal transduction, Cancer therapy, Ras oncogenes, Raf-1 kinase, Ral-GDP dissociation stimulator, Phosphatidylinositol 3-kinase, Farnesyltransferase inhibitors, Choline kinase inhibitors