biostudies-literatureNusrat MNCI NIH HHSNational Institutes of Health102343https://www.ebi.ac.uk/biostudies/studies/S-EPMC9908842biostudies-literatureUnknown68About half of colorectal cancers harbor mutations in the KRAS gene. The presence of these mutations is associated with worse prognosis and, until now, the absence of matched targeted therapy options. In this review, we discuss clinical efforts to target KRAS in colorectal cancer from studies of downstream inhibitors to recent direct inhibitors of KRAS^G12C and other KRAS mutants. Early clinical trial data, however, suggest more limited activity for these novel inhibitors in colorectal cancer compared to other cancer types, and we discuss the role of receptor tyrosine kinase signaling and parallel signaling pathways in modulating response to these inhibitors. We also review the effect of KRAS mutations on the tumor-immune microenvironment and efforts to induce an immune response aCurrent opinion in pharmacologyKRAS inhibition in metastatic colorectal cancer: An update.PMC9908842P30 CA008748P30 CA08748Nusrat MYaeger RfalseKRAS inhibition in metastatic colorectal cancer: An update.About half of colorectal cancers harbor mutations in the KRAS gene. The presence of these mutations is associated with worse prognosis and, until now, the absence of matched targeted therapy options. In this review, we discuss clinical efforts to target KRAS in colorectal cancer from studies of downstream inhibitors to recent direct inhibitors of KRAS^G12C and other KRAS mutants. Early clinical trial data, however, suggest more limited activity for these novel inhibitors in colorectal cancer compared to other cancer types, and we discuss the role of receptor tyrosine kinase signaling and parallel signaling pathways in modulating response to these inhibitors. We also review the effect of KRAS mutations on the tumor-immune microenvironment and efforts to induce an immune response a2023-01-01T00:00:00Z2023 Feb2025-04-26T11:51:58.427Z2025-02-19T04:59:41.467ZS-EPMC99088423663874210.1016/j.coph.2022.102343