Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer

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Abstract
Significance: Resistance to treatment with endocrine therapy occurs in ∼50% of all breast cancer patients. The pathway(s) leading to drug resistance is ill-defined. We show that accessibility to the genome is altered in drug-resistant compared with responsive breast cancer cells. This coincides with the overactivation of the NOTCH pathway in drug-resistant compared with responsive cancer cells. The transcription factor PBX1, a known NOTCH target gene, is required for the growth of endocrine therapy-resistant breast cancer cells. Accordingly, a gene expression signature based on NOTCH-PBX1 activity can discriminate a priori breast cancer patients that are responsive or not to endocrine therapy.

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