Getting a handle on KRAS inhibitor resistance with hapten-mediated anti-tumor immunity.

Covalent inhibitors of oncogenic KRAS ^G12C have demonstrated impressive clinical responses; however, therapeutic resistance has been commonly observed. In this issue, Zhang and colleagues demonstrate that small molecule KRAS ^G12C inhibitors can generate haptenated major histocompatibility complex (MHC) class I:peptide complexes, which represent attractive targets for immune-based therapies to combat pharmacologic resistance.
Competing Interests: Declaration of interests A.J.A. has consulted for Arrakis Therapeutics, Syros Pharmaceuticals, Boehringer Ingelheim, T-knife Therapeutics, AstraZeneca, Mirati Therapeutics, Revolution Medicines, Anji Pharmaceuticals, and Merck & Co., Inc. A.J.A. consults for and holds equity in Riva Therapeutics. A.J.A. has research funding from Mirati Therapeutics, Syros Pharmaceuticals, Bristol Myers Squibb, Revolution Medicines, Novartis, Novo Ventures and Deerfield, Inc. W.A.F-P. has consulted for PMV Pharma and holds equity in Regeneron. W.A.F-P. receives research support from Arcus Biosciences and Apexigen.
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