Progress in precision therapy targeting KRAS gene mutations in pancreatic cancer

KRAS mutations are the core driving events in the initiation and progression of pancreatic cancer. Due to its unique structure and high affinity for guanosine triphosphate, KRAS has long been considered "undruggable". In recent years, with the development of structural biology and medicinal chemistry, targeted therapies for KRAS G12C, G12D mutations, and pan‑KRAS/RAS have emerged, reshaping the treatment landscape of pancreatic cancer. By combining the latest research progress both domestically and internationally along with clinical experience, the authors systema-tically explain the evolution of KRAS‑targeted therapy from "single‑point mutation targeting" to "whole signal network regulation". They also explore the core mechanisms of compensatory resistance in targeted therapy and discusses potential future combination therapy strategies, aiming to advance the precision treatment of pancreatic cancer from theoretical possibilities to clinical feasibility.