Article
ESR1 mutations and CDK4/6 inhibitor choice shape clonal selection and adaptive cell states during acquired resistance.
Genome medicine - 27 Jun 2026
Guarducci Cristina, Abravanel Daniel, Russo Douglas, Prasad Kavya, Fu Jingxin, Nagy Zsuzsanna, Rao Vishwajit, Nardone Agostina, Kuang Yanan, Feit Avery, Ma Wen, Feit Gabriella Cohen, Hermida-Prado Francisco, Heraud Capucine, Munoz Gomez Miguel, Garcia Cortes Diana Elisa, Kurnia Patrick, Gomez Tejeda Zanudo Jorge, Li Rong, Qiu Xintao, Cristea Simona, Feiglin Ariel, Cheng Yu-Chen, Lin Nancy U, Tolaney Sara M, Malorni Luca, Sicinski Piotr, Polyak Kornelia, Paweletz Cloud, Long Henry, Stewart Chip, Michor Franziska, Getz Gad, Brown Myles, Jeselsohn Rinath
Abstract excerpt
BACKGROUND: In estrogen receptor-positive (ER +) breast cancer, CDK4/6 inhibitors (CDK4/6is) combined with endocrine therapy (ET) are standard first-line treatment for metastatic disease. However, most patients eventually develop resistance. Activating ESR1 mutations are a prevalent mechanism of acquired resistance to ET and are enriched after ET plus a CDK4/6 inhibitor (CDK4/6i), but their role in the clonal...
Read the complete abstract on PubMedTopics
- Humans
- Estrogen Receptor alpha
- Cyclin-Dependent Kinase 6