title: Molecular pathways: targeting the kinase effectors of RHO-family GTPases.
abstract: RHO GTPases, members of the RAS superfamily of small GTPases, are adhesion and growth factor-activated molecular switches that play important roles in tumor development and progression. When activated, RHO-family GTPases such as RAC1, CDC42, and RHOA, transmit signals by recruiting a variety of effector proteins, including the protein kinases PAK, ACK, MLK, MRCK, and ROCK. Genetically induced loss of RHO function impedes transformation by a number of oncogenic stimuli, leading to an interest in developing small-molecule inhibitors that either target RHO GTPases directly, or that target their downstream protein kinase effectors. Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use, their potential value as cancer therapeutics continues to facilitate pharmaceutical research and development and is a promising therapeutic strategy.
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Tatiana Y
authors.initials: TY
authors.lastname: Prudnikova
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Sonali J
authors.initials: SJ
authors.lastname: Rawat
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Jonathan.Chernoff@fccc.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
mesh_terms: D063646:Carcinogenesis; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000627:therapeutic use; D015398:Signal Transduction / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000627:therapeutic use
chemical_list: D010770:Phosphotransferases; D020741:rho GTP-Binding Proteins