Aumilto Silva, Medical Oncologist and Clinical Research at Hospital Santa Catarina Paulista, shared a post on X:
“This Cancer Discovery study shows:
- Tumors contain HER2-high and HER2-low subclones with shared origin but distinct behavior
- HER2-low cells drive resistance to ADCs
- These cells remain sensitive to HER2 TKIs
Biologically:
- Subclonal cooperation promotes tumor fitness
- ADC treatment selects for HER2-low populations – recurrence
- Limited ‘bystander effect’ depends on payload sensitivity
Take-home:
- Consider HER2 heterogeneity as a predictive resistance mechanism
- Supports rational combinations rather than sequential HER2-targeted therapy. “
Title: HER2 heterogeneous breast cancer models reveal novel therapeutic targets and subclonal dynamics during evolution to resistance to HER2-targeted therapies
Authors: Marie-Anne Goyette, Christopher Graser, Marco Seehawer, Andriana Patmanidis, Ernesto Rojas Jimenez, Avni Kamat, Pengze Yan, Anne Fassl, Pierre Foidart, Zheqi Li, Ameera James, George Sflomos, Cathrin Brisken, Piotr Sicinski, Franziska Michor, Kornelia Polyak
Read the Full Article.
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