{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:33:26Z","timestamp":1790681606283,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stand Up to Cancer Foundation, and Stand Up to Cancer Foundation\/The V Foundation","award":["D2015-039 and D2015\u2010037"],"award-info":[{"award-number":["D2015-039 and D2015\u2010037"]}]},{"name":"National Science Foundation grants","award":["PHY 1545832, PHY 1545839 and 1545853"],"award-info":[{"award-number":["PHY 1545832, PHY 1545839 and 1545853"]}]},{"name":"Ministerio de Economia y Competitividad","award":["RYC-2015-18357"],"award-info":[{"award-number":["RYC-2015-18357"]}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-094533-A-I00"],"award-info":[{"award-number":["RTI2018-094533-A-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008050","name":"CELLEX foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CERCA Programme \/ Generalitat de Catalunya","award":["2017 SGR 1079"],"award-info":[{"award-number":["2017 SGR 1079"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Breast cancer is the most frequent type of cancer and the major cause of mortality in women. The rapid development of various therapeutic options has led to the improvement of treatment outcomes; nevertheless, one-third of estrogen receptor (ER)-positive patients relapse due to cancer cell acquired resistance. Here, we use dynamic BH3 profiling (DBP), a functional predictive assay that measures net changes in apoptotic priming, to find new effective treatments for ER+ breast cancer. We observed anti-apoptotic adaptations upon treatment that pointed to metronomic therapeutic combinations to enhance cytotoxicity and avoid resistance. Indeed, we found that the anti-apoptotic proteins BCL-xL and MCL-1 are crucial for ER+ breast cancer cells resistance to therapy, as they exert a dual inhibition of the pro-apoptotic protein BIM and compensate for each other. In addition, we identified the AKT inhibitor ipatasertib and two BH3 mimetics targeting these anti-apoptotic proteins, S63845 and A-1331852, as new potential therapies for this type of cancer. Therefore, we postulate the sequential inhibition of both proteins using BH3 mimetics as a new treatment option for refractory and relapsed ER+ breast cancer tumors.<\/jats:p>","DOI":"10.3390\/cells10071659","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T10:06:34Z","timestamp":1625220394000},"page":"1659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins"],"prefix":"10.3390","volume":"10","author":[{"given":"Clara","family":"Alcon","sequence":"first","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge G\u00f3mez Tejeda","family":"G\u00f3mez Tejeda Za\u00f1udo","sequence":"additional","affiliation":[{"name":"Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9485-0828","authenticated-orcid":false,"given":"Reka","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Biology, The Pennsylvania State University, University Park, PA 16802-6300, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-9438","authenticated-orcid":false,"given":"Nikhil","family":"Wagle","sequence":"additional","affiliation":[{"name":"Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Scaltriti","sequence":"additional","affiliation":[{"name":"Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-9013","authenticated-orcid":false,"given":"Anthony","family":"Letai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-3679","authenticated-orcid":false,"given":"Josep","family":"Samitier","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"},{"name":"Department of Electronics and Biomedical Engineering, University of Barcelona (UB), 08028 Barcelona, Spain"},{"name":"Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Montero","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.rpor.2013.12.003","article-title":"Breast cancer: Actual methods of treatment and future trends","volume":"19","author":"Murawa","year":"2014","journal-title":"Rep. 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