title: The renewed battle against RAS-mutant cancers.
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.
authors.affiliation: Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore. jitkong.cheong@duke-nus.edu.sg.
authors.forename: Jit Kong
authors.identifier: http://orcid.org/0000-0002-2658-5436
authors.initials: JK
authors.lastname: Cheong
mesh_terms: D000818:Animals; D001343:Autophagy; D002471:Cell Transformation, Neoplastic; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006160:Guanosine Triphosphate; D018631:ras Proteins
keywords: Autophagy; Cancer therapeutics; HRAS; KRAS; Kinases; NRAS; Signaling; Small GTPases