Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 1, Pages 24-29Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-0827
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Funding
- NIH [R01CA148805, R01CA098830]
- Department of Defense [NF130108]
- Children's Tumor Foundation
- state of Pennsylvania [P30CA006927]
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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. (C) 2014 AACR.
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