biostudies-literatureXu YNational Cancer Institute (NCI)NCRR NIH HHSNIDDK NIH HHSNHLBI NIH HHSNIOSH CDC HHSNational Cancer InstituteNHGRI NIH HHSNCI NIH HHS1640-1652https://www.ebi.ac.uk/biostudies/studies/S-EPMC12475887biostudies-literatureUnknown24(10)Diffuse mesothelioma is a rare but highly aggressive and treatment-resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid cell leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are antiapoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance. We investigated whether B-cell homology domain3 profiles were consistent between intra-patient fresh tumor sample, patient-derived cells, and patient-derived xenografts (PDX) by B-cell homology domain-3 profiling; we observed striking consistency which enabled cross-model comparisons. Next, we co-targeted BCL-xl and MCL-1 and noted thatMolecular cancer therapeuticsCo-Targeting BCL-xL with MCL-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.PMC12475887R37 CA289419UM1 HG006348R01 DK114356R03 CA252685-01R21 CA256466U01 CA214195R01 CA290173S10 RR024574R03 CA252685U24 OH009077P30 CA125123R01 HL130249Vilchis MZhu YRipley RTHilsenbeck SGSurman DRAggison JCShen YHLi NRamineni MLi YMedina CGWu SChen XDobrolecki LEXu YfalseCo-Targeting BCL-xL with MCL-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.Diffuse mesothelioma is a rare but highly aggressive and treatment-resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid cell leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are antiapoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance. We investigated whether B-cell homology domain3 profiles were consistent between intra-patient fresh tumor sample, patient-derived cells, and patient-derived xenografts (PDX) by B-cell homology domain-3 profiling; we observed striking consistency which enabled cross-model comparisons. Next, we co-targeted BCL-xl and MCL-1 and noted that2025-01-01T00:00:00Z2025 Oct2026-06-06T17:45:20.886Z2026-06-03T03:10:45.195ZS-EPMC124758874080477310.1158/1535-7163.mct-24-087310.1158/1535-7163.MCT-24-0873