Determinants of sensitivity to HER2-targeted antibody drug conjugates in urothelial cancer.

ABSTRACT: HER2, encoded by the ERBB2 gene, is a receptor tyrosine kinase frequently activated in human cancers via gene amplification, mutation, and/or protein overexpression. In an analysis of 42,415 prospectively analyzed solid tumors, we show that 14.5% of urothelial cancers (n = 295/2,035) have oncogenic or likely oncogenic ERBB2 alterations (6.7% ERBB2 mutation, 6.3% amplification of wildtype ERBB2, and 1.5% concurrent mutation and amplification). Discordance of ERBB2 mutational status between primary and metastatic disease sites is common in patients with urothelial cancer as is discordance of ERBB2 mutational status between patient-derived organoid/xenograft models and the tumors from which they were derived. In patient-derived urothelial cancer models, the HER2-targeted antibody-drug conjuga

SUBMITTER: Chen Z 

PROVIDER: S-EPMC12830848 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature