title: Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?
abstract: There is now considerable and increasing evidence for a causal role for aberrant activity of the Ras superfamily of small GTPases in human cancers. These GTPases function as GDP-GTP-regulated binary switches that control many fundamental cellular processes. A common mechanism of GTPase deregulation in cancer is the deregulated expression and/or activity of their regulatory proteins, guanine nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound state and GTPase-activating proteins (GAPs) that return the GTPase to its GDP-bound inactive state. In this Review, we assess the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.
authors.affiliation: University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Department of Pharmacology, Chapel Hill, North Carolina 27599, USA.
authors.forename: Dominico
authors.initials: D
authors.lastname: Vigil
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cherfils
authors.forename: Kent L
authors.initials: KL
authors.lastname: Rossman
authors.forename: Channing J
authors.initials: CJ
authors.lastname: Der
mesh_terms: D000818:Animals; D020126:Brefeldin A / Q000627:therapeutic use; D055808:Drug Discovery; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
chemical_list: C489850:ECT2 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C453280:PREX1 protein, human; D011518:Proto-Oncogene Proteins; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D020126:Brefeldin A