{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:09:13Z","timestamp":1790168953446,"version":"4.1.0"},"reference-count":311,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["TEC\u2010128089"],"award-info":[{"award-number":["TEC\u2010128089"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","award":["706679"],"award-info":[{"award-number":["706679"]}],"id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>Breast cancer remains a leading cause of death among women, with the majority of mortality being attributed to metastatic disease and acquisition of therapeutic resistance. Epigenetic\u2010driven plasticity in breast cancer cells is a critical mediator of breast cancer progression and remains a leading challenge for effective treatment. Broadly, we categorize breast cancer plasticity into four interconnected processes: (a) development of cancer stem cell traits, (b) epithelial\u2010to\u2010mesenchymal transition (EMT), (c) luminal\u2010to\u2010basal lineage switching, and (d) acquisition of therapeutic resistance and recurrence. Here, we first assess the evidence supporting the cell of origin for breast cancer subtypes, which are directly influenced by distinct chromatin landscapes, and can impact cellular state during breast cancer initiation. Then, we highlight well\u2010documented epigenetic regulatory mechanisms and associated epigenetic regulators which can dictate these four processes to drive breast cancer plasticity. In particular, we discuss recent evidence that epigenetic therapies, or epidrugs, can induce basal\u2010to\u2010luminal switching, termed redifferentiation. This approach can be exploited to restore therapeutic sensitivity in basal\u2010like and aggressive HER2\u2010driven breast cancers, therefore presenting as viable strategies in combination with standard of care therapeutics. We conclude with anticipated future directions in targeting cell plasticity as a therapeutic strategy and offer new opportunities for drug development.<\/jats:p>","DOI":"10.1111\/febs.70740","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:55:23Z","timestamp":1790168123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic control of cellular plasticity in breast cancer progression"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0124-1546","authenticated-orcid":false,"given":"Ellie J.","family":"Massey","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Health Sciences McGill University  Montreal Canada"},{"name":"Goodman Cancer Institute, Faculty of Medicine and Health Sciences McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2394-2647","authenticated-orcid":false,"given":"Elizabeth","family":"Podleszanski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Health Sciences McGill University  Montreal Canada"},{"name":"Goodman Cancer Institute, Faculty of Medicine and Health Sciences McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-4166","authenticated-orcid":false,"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Health Sciences McGill University  Montreal Canada"},{"name":"Goodman Cancer Institute, Faculty of Medicine and Health Sciences McGill University  Montreal 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