KRAS Inhibitors: Targeting the 'Undruggable' Mutation in 2026 and Beyond
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Once deemed "undruggable" due to its smooth surface and high affinity for GTP, the KRAS oncogene has become a prime target in precision oncology. KRAS mutations drive approximately 20-30% of all cancers, with high prevalence in non-small cell lung cancer (NSCLC, ~30%), colorectal cancer (CRC, ~40%), and pancreatic ductal adenocarcinoma (PDAC, >90%). The most common mutation historically was G12C, but breakthroughs now extend to G12D, G12V, and multi-selective "pan-KRAS" approaches. Update: KRAS Inhibitors: Targeting the 'Undruggable' Mutation in 2026 and Beyond Key Breakthroughs in KRAS G12C Inhibitors The pioneering covalent inhibitors sotorasib (Lumakras) and adagrasib (Krazati), approved earlier for KRAS G12C-mutated NSCLC, saw major expansions in 2025: January 2025 FDA approval : Sotorasib combined with panitumumab (Vectibix, an EGFR inhibitor) for previously treated KRAS G12C-mutated metastatic CRC. This combination addresses adaptive resistance via ...