Different Diseases, Different Escapes: Trastuzumab Deruxtecan Resistance in HER2-Amplified versus HER2-Low Breast Cancer
Abstract
In this issue of Cancer Discovery, Chen and colleagues demonstrate that, in preclinical models, HER2 expression level directly affects trastuzumab deruxtecan internalization and cytotoxicity, with clinical data revealing divergent target dynamics depending on whether HER2 functions as an oncogenic driver or a dispensable antigen. Together with prior preclinical and clinical evidence, these findings support a context-dependent model in which target downregulation predominates in HER2-low disease, whereas payload resistance or rare binding-site mutations may dominate resistance in HER2-addicted tumors, with important implications for antibody-drug conjugate selection and sequencing. See related article by Chen et al., p. 235.
Fields of Study & Subjects
HER2/EGFR in Cancer Research
Monoclonal and Polyclonal Antibodies Research
Advanced Biosensing Techniques and Applications
Publication details
- Journal / source
- Cancer Discovery
- Publisher
- American Association for Cancer Research (AACR)
- Volume
- 16
- Issue
- 2
- Pages
- 195–197
- Publication date
- 6 February 2026
- Language
- EN