Kirsten rat sarcoma virus (KRAS) is one of the prevalent oncogenic drivers in gastrointestinal (GI) cancers, including pancreatic ductal adenocarcinoma and colorectal cancer. The KRAS protein is a GTPase that activates several signaling pathways involved in cancer survival. Although KRAS mutations have long been considered difficult to target, recent advances have led to the development of small-molecule inhibitors targeting the mutations, particularly KRAS G12C. These inhibitors are showing promise in GI cancers. This review explores the molecular biology of KRAS mutations, their prevalence in GI malignancies, the current therapeutic approaches targeting KRAS, ongoing clinical trials, the challenges associated with resistance, and future directions for KRAS-targeted therapies in GI cancers.
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