Fig. 1: Subset of PCa tumors is responsive to single-agent BCL-XL inhibition.

A BH3 mimetic screening in PCa 2D and 3D models. Growth inhibition of PCa models treated for 4 days with single agent Navitoclax (BCL-XL inhibitor), Venetoclax (BCL-2 inhibitor), or S63845 (MCL-1 inhibitor) over a dose range was assessed compared to control. The fraction of models that could be inhibited by >50% for each treatment at the highest concentration (1 μM) is shown. Left panel created in Biorender, Yuan, X. (2025) https://BioRender.com/r54j854B Heat map based on ranking of IC50 values showing distribution of PCa model sensitivity to BH3 mimetics. C BIDPC5 spheroids were treated with navitoclax and S63845 for 6 h. Apoptosis was assessed with luminescence-based caspase 3 and 7 activity assay. Mean and SEM for 5 biological replicates are shown. Data were analyzed by one-way ANOVA ***p < 0.001. D BIDPC5 (navitoclax sensitive) and BIDPC4 (navitoclax resistant) spheroids were treated with navitoclax (1 μM) for 6 h. Apoptosis markers cleaved PARP and cleaved caspase 3 (CC3) were assessed with immunoblotting. E BIDPC5 spheroids were treated with navitoclax (1 μM) for 6 h. Apoptosis was assessed with fluorescence-based caspase 3 and 7 activity assay. Scale bar is 100 μM (F) BIDPC1 and BIDPC5 patient derived xenografts were treated with intraperitoneal DMSO or navitoclax (50 mg/kg every other day) for 14 days. Fold change in tumor volume was assessed after completion to therapy. Asterisk (*) represents mice that developed toxicity requiring euthanasia during the 14 day treatment period. Data were analyzed by unpaired t-test ***p < 0.001 (for PC1 p = 0.0001 and for PC5 p = 0.0008). Upper panel was created in Biorender. Yuan, X. (2025) https://BioRender.com/f87k274G Kaplan-Meyer curves show overall survival. Data were analyzed by logrank test. Data are presented as mean values +/- SEM. Source data are provided as a Source Data file.