KRASG12C: finally a target in colorectal cancer?

By Ana Espino | Published on March 24, 2026 | 3 min read


Metastatic colorectal cancer (mCRC) remains associated with a poor prognosis, with a 5-year survival rate below 20%. Despite advances in combination chemotherapy and anti-VEGF or anti-EGFR antibodies, therapeutic options remain limited after failure of standard treatment lines.

KRAS mutations occur in approximately 40% of mCRC cases. Among these, the KRASG12C mutation—present in 3–4% of patients—is associated with aggressive tumor biology and resistance to anti-EGFR therapies. Historically, KRAS was considered “undruggable” due to its high affinity for GTP.  

The identification of a specific pocket in the G12C mutant has enabled the development of selective covalent inhibitors. This review, published in Future Oncology (2025), analyzes the pharmacological, clinical, and regulatory data on adagrasib, as well as its strategic positioning in mCRC.