{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:09:13Z","timestamp":1760123353879,"version":"3.41.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370776","92357301","32170736"],"award-info":[{"award-number":["32370776","92357301","32170736"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YD9100002011"],"award-info":[{"award-number":["YD9100002011"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The Aurora\u2010A kinase inhibitor MLN8237 has shown efficacy in clinical trials for advanced breast cancer; however, its use as a monotherapy is limited by significant side effects and modest efficacy. Therefore, combining MLN8237 with other agents at lower doses may provide a viable alternative. In this study, we evaluated the combination of MLN8237 with the BH3 mimetic ABT263 for the treatment of triple\u2010negative breast cancer (TNBC). We found that this combination significantly suppressed tumor growth and metastasis in immunocompetent syngeneic mouse models, whereas its efficacy was attenuated in immunodeficient xenograft models. Mechanistic studies revealed that the combination enhanced anti\u2010tumor immunity by increasing the presence of CD8<jats:sup>+<\/jats:sup> T cells and NK cells, while reducing the number of immunosuppressive cells in the tumor microenvironment. This shift resulted in elevated levels of IFN\u2010\u03b3 and granzyme B, which activated the extrinsic apoptotic pathways in cancer cells. Notably, the combination treatment did not affect tumor cell proliferation but promoted apoptosis with minimal toxicity. Furthermore, the synergistic effect of MLN8237 and ABT263 in inducing intrinsic apoptosis was primarily driven by the inhibition of the AKT\u2010Mcl\u20101 and Bcl\u2010xL survival pathways in cultured tumor cells. Together, these findings support the MLN8237\u2010ABT263 combination as an effective treatment strategy for TNBC, promoting both immune\u2010mediated extrinsic apoptosis and inactivation of Bcl\u2010xL\/Mcl\u20101\u2010dependent intrinsic anti\u2010apoptotic pathways.<\/jats:p>","DOI":"10.1111\/cas.70072","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:17:38Z","timestamp":1743466658000},"page":"1823-1835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dual Targeting of Aurora\u2010A and Bcl\u2010<scp>xL<\/scp> Synergistically Reshapes the Immune Microenvironment and Induces Apoptosis in Breast Cancer"],"prefix":"10.1111","volume":"116","author":[{"given":"Mingxue","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ultrasound, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei China"},{"name":"Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei China"},{"name":"Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei 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