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Roles of Rho/ROCK in Cancer Signaling

  • Yesim Gökmen-Polar
Chapter

Abstract

The members of Rho/ROCK signaling pathway are well-established regulators of actin cytoskeleton and dynamics. Accumulating evidence demonstrates their key roles in other biological processes including polarity, motility, invasion, cell cycle progression, and survival. Aberrant Rho/ROCK signaling have been implicated in both preclinical and clinical samples of several cancers. Mutations of Rho GTPases and ROCK isoforms (ROCK1 and ROCK2) have been reported in tumor samples. In addition, their elevated expression levels have been associated with poor outcome in those tumors. Therefore, Rho/ROCK family genes serve as promising candidates for therapeutic targeting in several cancers. This review focuses on the recent progress in therapeutic targeting of the Rho/ROCK signaling pathway in cancer. In particular, we focus on the potential utility of inhibitors of ROCK, downstream effectors of Rho GTPases, as they have been considered more specific to inhibit Rho/ROCK activity. Although no effective drugs targeting Rho/ROCK activity are available for the clinical management of cancer, studies using drugs that pharmacologically inhibit ROCK isoforms suggest a promising future. AT13148, an inhibitor of members of AGC kinase family including ROCK1 and ROCK2, is in phase 1 clinical trial initiated in 2012 for the treatment of advanced solid tumors (ClinicalTrials.gov identifier NCT01585701). A deeper understanding of this pathway using isoform-specific inhibitors of Rho kinases (ROCK1 and ROCK2) may add new treatment options for future precision cancer therapy improving the clinical utility of this pathway.

Keywords

Rho GTPases ROCK ROCK1 ROCK2 Cancer ROCK inhibitors 

Notes

Conflict of Interest

The author has no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineIndiana University School of MedicineIndianapolisUSA

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