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Chromatin and disease

Switching under selection: how CoREST controls endocrine therapy resistance in ER+ breast cancer

Nature Structural & Molecular Biology volume 29, pages 1040–1042 (2022)Cite this article

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New research shows that the CoREST complex controls the acquisition of endocrine therapy resistance in estrogen receptor-positive breast cancers. Profiling data show that this resistance transition is accompanied by a functional retargeting of CoREST on chromatin in coordination with cJUN and SWI/SNF (cBAF).

Despite advancements in research and treatment, breast cancer continues to be a leading cause of human cancer cases and deaths worldwide1. The predominant class of breast cancers express the estrogen receptor (ER+) and respond well to endocrine therapy (such as ERα blockade, estrogen synthesis inhibition and selective ERα degradation), with a 5-year overall survival rate of around 90%2. However, these hormonal interventions strongly select for therapy-resistant tumors, as seen in the 40% of cases in which resistance arises after 5 years of treatment3. Therefore, a central challenge in treating ER+ breast cancers is the molecular characterization of endocrine therapy resistance and the identification of therapeutic strategies that circumvent breast cancer metastatic reprogramming.

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Fig. 1: CoREST coordinates the conversion of therapy-sensitive to therapy-resistant states via a functional switch in binding partners in estrogen-deprived T47D cells.

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Acknowledgements

B.Y.C. and D.C.H. are supported by US National Institutes of Health grants 5T32GM133351 (B.Y.C), R01 CA228211 (D.C.H.), the Pew-Stewart Scholars for Cancer Research (D.C.H.) and the American Cancer Society Research Scholar Award (D.C.H.)

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  1. Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

    Brent Y. Chick & Diana C. Hargreaves

  2. Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA

    Brent Y. Chick

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  1. Brent Y. Chick
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  2. Diana C. Hargreaves
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Correspondence to Diana C. Hargreaves.

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Chick, B.Y., Hargreaves, D.C. Switching under selection: how CoREST controls endocrine therapy resistance in ER+ breast cancer. Nat Struct Mol Biol 29, 1040–1042 (2022). https://doi.org/10.1038/s41594-022-00858-9

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