Computational and Functional Analyses of HER2 Mutations Reveal Allosteric Activation Mechanisms and Altered Pharmacologic Effects

• Published in: Cancer research (Chicago, Ill.) Vol. 83; no. 9; pp. 1531 - 1542
• Main Authors: Ishiyama, Noboru, O'Connor, Matthew, Salomatov, Andrei, Romashko, Darlene, Thakur, Shalabh, Mentes, Ahmet, Hopkins, Julia F., Frampton, Garrett M., Albacker, Lee A., Kohlmann, Anna, Roberts, Christopher, Buck, Elizabeth
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 02.05.2023
• Subjects: Adenosine Triphosphate; Allosteric Regulation; Computational Cancer Biology and Technology; Humans; Mutation; Neoplasms - genetics; Protein Kinase Inhibitors - pharmacology; Quinazolines - pharmacology; Receptor, ErbB-2 - metabolism

Amplification of HER2 can drive the proliferation of cancer cells, and several inhibitors of HER2 have been successfully developed. Recent advances in next-generation sequencing now reveal that HER2 is subject to mutation, with over 2,000 unique variants observed in human cancers. Several examples o...