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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Should we keep rocking? Portraits from targeting Rho kinases in cancer

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Author(s):
de Sousa, Graziella Ribeiro [1] ; Vieira, Gabriela Maciel [1] ; das Chagas, Pablo Ferreira [1] ; Pezuk, Julia Alejandra [2] ; Brassesco, Maria Sol [3]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Sao Paulo - Brazil
[2] Anhanguera Univ Sao Paulo, UNIAN SP, Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Biol, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PHARMACOLOGICAL RESEARCH; v. 160, OCT 2020.
Web of Science Citations: 1
Abstract

Cancer targeted therapy, either alone or in combination with conventional chemotherapy, could allow the survival of patients with neoplasms currently considered incurable. In recent years, the dysregulation of the Rhoassociated coiled-coil kinases (ROCK1 and ROCK2) has been associated with increased metastasis and poorer patient survival in several tumor types, and due to their essential roles in regulating the cytoskeleton, have gained popularity and progressively been researched as targets for the development of novel anti-cancer drugs. Nevertheless, in a pediatric scenario, the influence of both isoforms on prognosis remains a controversial issue. In this review, we summarize the functions of ROCKs, compile their roles in human cancer and their value as prognostic factors in both, adult and pediatric cancer. Moreover, we provide the up-to-date advances on their pharmacological inhibition in pre-clinical models and clinical trials. Alternatively, we highlight and discuss detrimental effects of ROCK inhibition provoked not only by the action on off-targets, but most importantly, by pro-survival effects on cancer stem cells, dormant cells, and circulating tumor cells, along with cell-context or microenvironment-dependent contradictory responses. Together these drawbacks represent a risk for cancer cell dissemination and metastasis after anti-ROCK intervention, a caveat that should concern scientists and clinicians. (AU)

FAPESP's process: 14/03877-3 - Evaluation of rock kinases and their interaction with microRNAs in bone sarcomas of childhood: implications for tumor progression and invasion
Grantee:María Sol Brassesco Annichini
Support Opportunities: Regular Research Grants