Therapeutic Targets of KRAS in Colorectal Cancer

Simple Summary Colorectal cancer is among the most common cancers in the United States. The advancement in treatment and early diagnosis have enabled a reduction in mortality from the disease among the patients with early and localized disease; however, the survival continues to be dismal in the metastatic colorectal cancers. Understanding the biological and genetic factors is crucial is making the therapeutic strategy and improving survival outcomes. One of such critical steps is the understanding of the mechanism and development of therapeutic targets against metastatic colorectal cancers bearing the KRAS mutation. Patients with metastatic colorectal cancer have a 5-year overall survival of less than 10%. Approximately 45% of patients with metastatic colorectal cancer harbor KRAS mutations. These mutations not only carry a predictive role for the absence of response to anti-EGFR therapy, but also have a negative prognostic impact on the overall survival. There is a growing unmet need for a personalized therapy approach for patients with KRAS-mutant colorectal cancer. In this article, we focus on the therapeutic strategies targeting KRAS- mutant CRC, while reviewing and elaborating on the discovery and physiology of KRAS.