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• W4386618085 endingPage "4481" @default.
• W4386618085 startingPage "4481" @default.
• W4386618085 abstract "Triple-negative breast cancer (TNBC) is an aggressive cancer that lacks specific molecular targets that are often used for therapy. The refractory rate of TNBC to broad-spectrum chemotherapy remains high; however, the combination of newly developed treatments with the current standard of care has delivered promising anti-tumor effects. One mechanism employed by TNBC to avoid cell death is the increased expression of the anti-apoptotic protein, myeloid cell leukemia 1 (MCL1). Multiple studies have demonstrated that increased MCL1 expression enables resistance to platinum-based chemotherapy. In addition to suppressing apoptosis, we recently demonstrated that MCL1 also binds and negatively regulates the transcriptional activity of TP73. TP73 upregulation is a critical driver of cisplatin-induced DNA damage response, and ultimately, cell death. We therefore sought to determine if the coadministration of an MCL1-targeted inhibitor with cisplatin could produce a synergistic response in TNBC. This study demonstrates that the MCL1 inhibitor, S63845, combined with cisplatin synergizes by inducing apoptosis while also decreasing proliferation in a subset of TNBC cell lines. The use of combined MCL1 inhibitors with cisplatin in TNBC effectively initiates TAp73 anti-tumor effects on cell cycle arrest and apoptosis. This observation provides a molecular profile that can be exploited to identify sensitive TNBCs." @default.
• W4386618085 created "2023-09-12" @default.
• W4386618085 creator A5030077585 @default.
• W4386618085 creator A5063669341 @default.
• W4386618085 date "2023-09-08" @default.
• W4386618085 modified "2023-10-17" @default.
• W4386618085 title "Myeloid Cell Leukemia 1 Small Molecule Inhibitor S63845 Synergizes with Cisplatin in Triple-Negative Breast Cancer" @default.
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• W4386618085 doi "https://doi.org/10.3390/cancers15184481" @default.
• W4386618085 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37760451" @default.
• W4386618085 hasPublicationYear "2023" @default.
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