Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer
- 1University of Illinois College of Medicine
Abstract
Up to 40% of patients with estrogen receptor positive breast cancer will experience relapse, either while on endocrine therapy (ET) or after ET is completed. A major contributor to ET failure is the presence of ET-insensitive cell populations within tumors. Here, we developed an analytical pipeline to systematically identify and target these populations by integrating single-cell RNA sequencing of ER+ tumors from the FELINE clinical trial with functional validation in a panel of patient-derived xenograft organoid models. We found that ET-insensitive cells are detected in all tumors regardless of clinical response and exhibit higher transcriptional heterogeneity than ET-sensitive populations. Using our pipeline, we identified and validated new therapeutic options that target patient-specific and shared ET-insensitive populations. Our integrated workflow provides a robust platform for identifying and targeting ET-insensitive cells and offers a translational framework to develop precision medicine approaches to improve outcome in breast cancer patients.
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BibTeX
@misc{semina2026integrative,
title = {{Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer}},
author = {S. Semina and R. J. Huggins and H. Zhao and K. Yanagihara and M. Sheinin and V. Macias and F. Alani and L. Feferman and A. A. Kajdacsy-Balla and D. Tonetti and K. Hoskins and J. Frasor and J. L. Coloff},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750719},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750719v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer
AU - S. Semina
AU - R. J. Huggins
AU - H. Zhao
AU - K. Yanagihara
AU - M. Sheinin
AU - V. Macias
AU - F. Alani
AU - L. Feferman
AU - A. A. Kajdacsy-Balla
AU - D. Tonetti
AU - K. Hoskins
AU - J. Frasor
AU - J. L. Coloff
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750719
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750719v1
AB - Up to 40% of patients with estrogen receptor positive breast cancer will experience relapse, either while on endocrine therapy (ET) or after ET is completed. A major contributor to ET failure is the presence of ET-insensitive cell populations within tumors. Here, we developed an analytical pipeline to systematically identify and target these populations by integrating single-cell RNA sequencing of ER+ tumors from the FELINE clinical trial with functional validation in a panel of patient-derived xenograft organoid models. We found that ET-insensitive cells are detected in all tumors regardless of clinical response and exhibit higher transcriptional heterogeneity than ET-sensitive populations. Using our pipeline, we identified and validated new therapeutic options that target patient-specific and shared ET-insensitive populations. Our integrated workflow provides a robust platform for identifying and targeting ET-insensitive cells and offers a translational framework to develop precision medicine approaches to improve outcome in breast cancer patients.
ER -