Rac1 as a therapeutic anticancer target: Promises and limitations.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Elsevier Science
      Original Publication: Oxford, New York [etc.] Paragamon Press.
    • Subject Terms:
    • Abstract:
      Small molecule inhibitors of GTPases are increasingly considered for the treatment of multiple human pathologies. The GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) plays major roles in vital cellular processes, notably in the control cell motility and dynamic, the regulation of oxidative stress, and in inflammatory and immune surveillance. As such, Rac1 is viewed as a potential target to combat cancers but also diverse inflammatory, metabolic, neurodegenerative, respiratory, cardiovascular, viral, and parasitic diseases. Potent and selective Rac1 inhibitors have been identified and designed, such as compounds GYS32661 and MBQ-167 both in preclinical development for the treatment of advanced solid tumors. The pleiotropic roles and ubiquitous expression of the protein can be viewed as limitations for anticancer approaches. However, the frequent overexpression and/or hyperactivation of the Rac1 in difficult-to-treat chemoresistant cancers, make Rac1 an attractive target in oncology. The key roles of Rac1 in multiple cellular pathways, together with its major implications in carcinogenesis, tumor proliferation and metastasis, support the development of small molecule inhibitors. The challenge is high and the difficulty shall not be underestimated, but the target is innovative and promising in combination with chemo- and/or immuno-therapy. Opportunities and challenges associated with the targeting of Rac1 are discussed.
      (Copyright © 2022 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cancer; Chemoresistance; GTPase; Immunotherapy; Rac1; Rac1 inhibitors
    • Accession Number:
      0 (RAC1 protein, human)
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
    • Publication Date:
      Date Created: 20220719 Date Completed: 20220824 Latest Revision: 20220914
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.bcp.2022.115180
    • Accession Number:
      35853497