Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer
Researchers identified a shared cancer vulnerability across prostate-cancer subtypes and showed early promise combining two drugs to reduce tumor cells in blood.
Integrating Vectra-based quantitative multiplex immunofluorescence, image mass cytometry, organoids, and xenograft models, BCL-2 was identified as a universal vulnerability across heterogeneous CRPC subtypes induced by AR pathway inhibitors (ARPIs). A Phase Ib clinical trial (NCT03751436) combining enzalutamide and the BCL-2 inhibitor venetoclax showed reduced circulating tumor cells in responders, providing early clinical validation of this combination strategy.
What the study was
- Study design
- Phase Ib clinical trial (NCT03751436) combined with single-cell imaging and preclinical mechanistic studies
- Population
- Castration-resistant prostate cancer patients; Phase Ib trial with enzalutamide + venetoclax
- Category
- Treatment Innovation
- Maturity
- Validated
- Journal
- Signal Transduction and Targeted Therapy
Why it surfaced
Phase Ib clinical trial validation of BCL-2 as a therapeutic target across heterogeneous CRPC with CTC monitoring; multi-platform mechanistic validation supports translational relevance. CRPC has high unmet need given treatment resistance. Published in high-impact Signal Transduction and Targeted Therapy.
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