Jean-Charles Soria, SVP and Oncology Therapeutic Area Head at Amgen, shared a post on X about a recent article by Wanyi Chen at al, published in Cancer Discovery:
“HER2-low tumors escape HER2 ADCs by losing the target
- True HER2 loss is uncommon in HER2-amplified disease but frequent in HER2-low, where HER2 isn’t oncogenic
- On HER2 ADC therapy, ~50% of tumors reduce HER2; among reducers, ~half become IHC 0
- Reduced HER2 → impaired ADC internalization, not payload resistance
- ERBB2 ECD variants disrupt antibody binding and phenocopy antigen loss
- Suggested strategy: multi-target payload delivery to bypass target dependence and improve durability
Title: Trastuzumab Deruxtecan Resistance via Loss of HER2 Expression and Binding
Authors: Wanyi Chen, Avantika Gupta, Nicholas Mai, Sharanya Nag, Joshua S. Lau, Sukrit Singh, John D. Chodera, Bo Liu, Elisa de Stanchina, Fresia Pareja, Atif Ali Hashmi, Miriam M. Lieberman, Shanu Modi, Jacqueline Bromberg, Pedram Razavi, Joshua Z. Drago, Sarat Chandarlapaty
Read the Full Article on Cancer Discovery
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