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The renewed battle against RAS-mutant cancers

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Abstract

The RAS genes encode for members of a large superfamily of guanosine-5′-triphosphate (GTP)-binding proteins that control diverse intracellular signaling pathways to promote cell proliferation. Somatic mutations in the RAS oncogenes are the most common activating lesions found in human cancers. These mutations invariably result in the gain-of-function of RAS by impairing GTP hydrolysis and are frequently associated with poor responses to standard cancer therapies. In this review, we summarize key findings of past and present landmark studies that have deepened our understanding of the RAS biology in the context of oncogenesis. We also discuss how emerging areas of research could further bolster a renewed global effort to target the largely undruggable oncogenic RAS and/or its activated downstream effector signaling cascades to achieve better treatment outcomes for RAS-mutant cancer patients.

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Acknowledgments

Space limitations preclude our manuscript from being a comprehensive review, and this unfortunately limits appropriate recognition of many of our colleagues worldwide, who have contributed immeasurably to the development of the RAS field. We thank David Virshup (Duke-NUS) for his critical review of our manuscript. This work was supported by an NMRC-CBRG New Investigator Grant (NMRC/BNIG/1078/2012) and a Duke-NUS-St. Baldrick’s Foundation Pediatric Cancer Research Fund (Duke-NUS-SBF/2015/0004) to JKC.

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  1. Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

    Fuquan Zhang & Jit Kong Cheong

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  1. Fuquan Zhang
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Correspondence to Jit Kong Cheong.

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Zhang, F., Cheong, J. The renewed battle against RAS-mutant cancers. Cell. Mol. Life Sci. 73, 1845–1858 (2016). https://doi.org/10.1007/s00018-016-2155-8

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