Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer

<jats:title>Abstract</jats:title><jats:p>Colorectal cancer (CRC) is a heterogeneous disease at the cellular and molecular levels. <jats:italic>Kirsten rat sarcoma</jats:italic> (<jats:italic>KRAS</jats:italic>) is a commonly mutated oncogene in CRC, with mutations in approximately 40% of all CRC cases; its mutations result in constitutive activation of the KRAS protein, which acts as a molecular switch to persistently stimulate downstream signaling pathways, including cell proliferation and survival, thereby leading to tumorigenesis. Patients whose CRC harbors <jats:italic>KRAS</jats:italic> mutations have a dismal prognosis. Currently, <jats:italic>KRAS</jats:italic> mutation testing is a routine clinical practice before treating metastatic cases, and the approaches developed to detect <jats:italic>KRAS</jats:italic> mutations have exhibited favorable sensitivity and accuracy. Due to the presence of <jats:italic>KRAS</jats:italic> mutations, this group of CRC patients requires more precise therapies. However, KRAS was historically thought to be an undruggable target until the development of KRAS<jats:sup>G12C</jats:sup> allele-specific inhibitors. These promising inhibitors may provide novel strategies to treat <jats:italic>KRAS</jats:italic>-mutant CRC. Here, we provide an overview of the role of KRAS in the prognosis, diagnosis and treatment of CRC.</jats:p>