KRAS 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 KRASG12C 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 against these tumors.

Automated summary

Approximately 50% of colorectal cancers have mutations in the KRAS gene, which are associated with worse prognosis and limited targeted therapy options. This review discusses clinical approaches to target KRAS in colorectal cancer, focusing on downstream inhibitors and recent direct inhibitors for KRASG12C and other mutants. Early clinical trial data indicates limited activity of these novel inhibitors compared to other cancer types, and the role of receptor tyrosine kinase signaling and parallel signaling pathways in modulating response to these inhibitors is explored. Additionally, the review examines the impact of KRAS mutations on the tumor-immune microenvironment and efforts to induce an immune response against these tumors.