Estrogen therapy induces receptor-dependent DNA damage enhanced by PARP inhibition in ER+ breast cancer.

Nicole A Traphagen Gary N Schwartz Steven Tau Alyssa M Roberts Amanda Jiang Sarah R Hosford Jonathan D Marotti Abigail E Goen Bianca A Romo Anneka L Johnson Emily-Claire K Duffy Eugene Demidenko Paul Heverly Yaron Mosesson Shannon M Soucy Fred Kolling Iv Todd W Miller

Published in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)

E2-induced ER activity drives DNA damage and growth inhibition in endocrine-resistant breast cancer cells. Inhibition of the DNA damage response using drugs such as PARP inhibitors can enhance therapeutic response to E2. These findings warrant clinical exploration of the combination of E2 with DNA damage response inhibitors in advanced ER+ breast cancer, and suggest that PARP inhibitors may synergize with therapeutics that exacerbate transcriptional stress.

Keyphrases

dna damage
dna damage response
dna repair
breast cancer cells
estrogen receptor
oxidative stress
endoplasmic reticulum
high glucose
diabetic rats
transcription factor
drug induced
endothelial cells
stem cells
bone marrow
heat stress
heat shock
replacement therapy
chemotherapy induced