Getting a handle on KRAS inhibitor resistance with hapten-mediated anti-tumor immunity
- PMID: 36099887
- DOI: 10.1016/j.ccell.2022.08.018
Getting a handle on KRAS inhibitor resistance with hapten-mediated anti-tumor immunity
Abstract
Covalent inhibitors of oncogenic KRASG12C have demonstrated impressive clinical responses; however, therapeutic resistance has been commonly observed. In this issue, Zhang and colleagues demonstrate that small molecule KRASG12C inhibitors can generate haptenated major histocompatibility complex (MHC) class I:peptide complexes, which represent attractive targets for immune-based therapies to combat pharmacologic resistance.
Copyright © 2022 Elsevier Inc. All rights reserved.
Conflict of interest statement
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.
Comment on
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A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy.Cancer Cell. 2022 Sep 12;40(9):1060-1069.e7. doi: 10.1016/j.ccell.2022.07.005. Cancer Cell. 2022. PMID: 36099883 Free PMC article.
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