Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.

ABSTRACT: Small molecule kinase inhibitors are critical in the modern treatment of cancers, evidenced by the existence of over 80 FDA-approved small-molecule kinase inhibitors. Unfortunately, intrinsic or acquired resistance, often causing therapy discontinuation, is frequently caused by mutations in the kinase therapeutic target. The advent of clinical tumor sequencing has opened additional opportunities for precision oncology to improve patient outcomes by pairing optimal therapies with tumor mutation profiles. However, modern precision oncology efforts are hindered by lack of sufficient biochemical or clinical evidence to classify each mutation as resistant or sensitive to existing inhibitors. Structure-based methods show promising accuracy in retrospective benchmarks at predicting whether a kina

SUBMITTER: Singh S 

PROVIDER: S-EPMC12038917 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature