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Overcoming Resistance to Drugs Targeting KRAS^G12C Mutation.

ABSTRACT: Activating KRAS mutations are present in 25% of human cancer. Although oncogenic Ras was deemed "undruggable" in the past, recent efforts led to the development of pharmacological inhibitors targeting the KRAS^G12C mutant, which have shown promise in early clinical trials. The development of allele-specific K-Ras^G12C inhibitors marked a new chapter in targeting oncogenic KRAS mutant in cancer. However, drug resistance against these new drugs will likely limit their efficacy in the clinic. Genome-wide approaches have been used to interrogate the mechanisms of resistance to K-Ras^G12C inhibitors, which would facilitate the development of therapeutics overcoming drug resistance. This article reviews the latest progress in resistance to K-Ras^G12C-targeted therapies and aims to provide insight in future research targeting drug resistance in cancer.

SUBMITTER: Jiao D

PROVIDER: S-EPMC7491749 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Overcoming Resistance to Drugs Targeting KRASG12C Mutation.

Jiao Delong D Yang Shengyu S

Innovation (Cambridge (Mass.)) 20200805 2

Activating KRAS mutations are present in 25% of human cancer. Although oncogenic Ras was deemed "undruggable" in the past, recent efforts led to the development of pharmacological inhibitors targeting the KRASG12C mutant, which have shown promise in early clinical trials. The development of allele-specific K-RasG12C inhibitors marked a new chapter in targeting oncogenic KRAS mutant in cancer. However, drug resistance against these new drugs will likely ...[more]

PMID: 32939510

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