Targeting KRAS Oncogene for Patients With Colorectal Cancer: A New Step Toward Precision Medicine.

Autor:	Sahin IH; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; University of Pittsburgh Medical Center, Pittsburgh, PA., Saridogan T; Hacettepe University School of Medicine, Ankara, Turkey., Ayasun R; Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY., Syed MP; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; University of Pittsburgh Medical Center, Pittsburgh, PA., Gorantla V; University of Pittsburgh Medical Center, Pittsburgh, PA., Malhotra M; University of Pittsburgh Medical Center, Pittsburgh, PA., Thomas R; University of Pittsburgh Medical Center, Pittsburgh, PA., Rhee J; University of Pittsburgh Medical Center, Pittsburgh, PA., Zhang J; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; University of Pittsburgh Medical Center, Pittsburgh, PA., Hsu D; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; University of Pittsburgh Medical Center, Pittsburgh, PA., Singhi AD; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; University of Pittsburgh Medical Center, Pittsburgh, PA., Saeed A; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; University of Pittsburgh Medical Center, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	JCO oncology practice [JCO Oncol Pract] 2024 Oct; Vol. 20 (10), pp. 1336-1347. Date of Electronic Publication: 2024 May 13.
DOI:	10.1200/OP.23.00787
Abstrakt:	KRAS mutations are common driver oncogenes associated with the development of several solid tumors. KRAS oncogene has been considered a highly challenging target for drug development because of structural features, including the lack of deep groove on its catalytic unit. However, by leveraging cysteine residues, covalent KRAS inhibitors irreversibly trap KRAS G12C mutants in their inactive GDP-bound state. These agents have resulted in significant clinical responses among patients with KRAS G12C-mutant solid tumors, including patients with colorectal cancer (CRC). Other allele-specific inhibitors of KRAS oncogene and panKRAS and panRAS inhibitors are also currently being investigated in clinical trials. This review article overviews recent clinical progress on KRAS G12C targeting for the management of patients with KRAS G12C-mutant CRC and provides an update on other RAS targeting approaches. We also discuss the unique biological features of RAS-mutant CRC, which require the combination of KRAS inhibitors and anti-epidermal growth factor receptor therapy, and elaborate on resistance mechanisms and novel therapeutic avenues that may define future treatment paradigms of patients with RAS-mutant CRC.
Databáze:	MEDLINE
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