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Review

Mechanistic Insight on Ras Inhibition Strategies in Cancer Therapy

Jeiran Pashapour-Anousheh ORCID logo, Abolfazl Barzegar, Mohammad Saeid Hejazi, Nikoo Hasheminejad, Hamid Reza Heidari, Elnaz Mehdizadeh Aghdam* ORCID logo

Abstract

Ras proteins are considered as one of the most critical cancer initiators. Mutations of this protein family lead to the continuous activation of the proliferation pathways. Therefore, many efforts have been taken to design the anti-mutant Ras drug candidates. Regardless of the development of promising inhibitors of Ras G12C mutant in a specific cancer type, there is no approved inhibitor of Ras mutants in the clinic. One of the significant limitations is to inhibit particular mutants and not to affect the wild-type Ras variants. Here we present a review on the mechanism of action of the Ras proteins to get a better insight into the strategies utilized to inhibit Ras-mutated cancers. The direct Ras inhibition strategies are then highlighted to obtain a better perspective of possible promising approaches to target Ras proteins in cancer therapy.
Keywords: RAS, Drug development, Cancer therapy, Structural drug design
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Submitted: 12 Dec 2020
Revision: 08 May 2021
Accepted: 08 May 2021
ePublished: 09 May 2021
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