ESR1 Mutation Status as a Biomarker for Radiation Response in ER-Positive Breast Cancer

Udden, Nashir; Wang, Q.; Alluri, Prasanna

doi:10.1016/j.ijrobp.2020.07.1066

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hotspot mutations in its ligand-binding domain occur in 30–40% of endocrine resistant breast tumors, promoting ligand-independent ER activation and metastasis 25 – 27 . Several recent studies showed that ESR1 mutant tumors are not only associated with endocrine resistance, but also gain unexpected resistance towards CDK4/6 inhibitors 28 , mTOR inhibitors 29 and radiation therapy 30 in a mutation subtype and context dependent manner, suggesting potentially more complex re-wiring of ER mutant tumors.…”

Section: Introductionmentioning

confidence: 99%

ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation

McGinn

et al. 2022

Nat Commun

View full text Add to dashboard Cite

Estrogen receptor alpha (ER/ESR1) is frequently mutated in endocrine resistant ER-positive (ER+) breast cancer and linked to ligand-independent growth and metastasis. Despite the distinct clinical features of ESR1 mutations, their role in intrinsic subtype switching remains largely unknown. Here we find that ESR1 mutant cells and clinical samples show a significant enrichment of basal subtype markers, and six basal cytokeratins (BCKs) are the most enriched genes. Induction of BCKs is independent of ER binding and instead associated with chromatin reprogramming centered around a progesterone receptor-orchestrated insulated neighborhood. BCK-high ER+ primary breast tumors exhibit a number of enriched immune pathways, shared with ESR1 mutant tumors. S100A8 and S100A9 are among the most induced immune mediators and involve in tumor-stroma paracrine crosstalk inferred by single-cell RNA-seq from metastatic tumors. Collectively, these observations demonstrate that ESR1 mutant tumors gain basal features associated with increased immune activation, encouraging additional studies of immune therapeutic vulnerabilities.

show abstract

Section: Introductionmentioning

confidence: 99%

ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation

McGinn

et al. 2022

Nat Commun

View full text Add to dashboard Cite

show abstract

ESR1 Mutation Status as a Biomarker for Radiation Response in ER-Positive Breast Cancer

Cited by 1 publication

References 0 publications

ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation

ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation

Contact Info

Product

Resources

About