Role of rat sarcoma virus mutations in cancer and potential target for cancer therapy

Abstract

The prevalence of oncogenic rat sarcoma virus (RAS) mutations has made RAS a popular target for cancer therapies. Significant discoveries have been reported regarding cancer molecular biology following the study of RAS mutations. These discoveries are integral in shaping the era of targeted cancer therapy, with direct targeting of RAS or downstream RAS effectors, such as Grb2 and MAPK a possibility. Novel agents such as farnesyltransferase directly bind and sequester RAS. While these new agents and approaches have shown promise in preclinical and clinical studies, the complexity of RAS signaling and the potential for robust adaptive feedback continue to present substantial challenges. Therefore, the development of targeted therapies will require a detailed understanding of the properties and dependencies of specific cancers to a RAS mutation. This review provides an overview of RAS mutations and their relationship with cancer and discusses their potential as therapeutic targets. Lay abstract: The widespread prevalence of cancer has focused research attention on the discovery and development of newer therapies. Significant discoveries regarding genetic mutations have provided new opportunities for development of targeted cancer therapies. In this review, mutations in the rat sarcoma virus protein are discussed along with their potential as targets for drug development.