Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7–Expressing CRPC Models
Using an unbiased, combinatorial, high-throughput drug screen, we identified the combination of co-targeting Bcl-xL and Mcl-1 to be highly synergistic across AR-V7-expressing CRPC models. We showed efficacy in higher-order models through validation across in vitro models spanning two-dimensional cell culture, three-dimensional cell culture, and a patient-derived organoid model. These findings identify a promising therapeutic strategy for patients with AR-V7-expressing CRPC.
Authors
- Kelli M. Wilson (ORCID: https://orcid.org/0000-0003-2636-2766)
- Erin Beck
- Andres F. Leon (ORCID: https://orcid.org/0009-0003-3187-6582)
- Craig J. Thomas (ORCID: https://orcid.org/0000-0001-9386-9001)
- Kinjal Bhadresha
- Xiaohu Zhang (ORCID: https://orcid.org/0000-0002-5872-4656)
- Keith Thomas Schmidt (ORCID: https://orcid.org/0009-0008-0285-0216)
- Jessica D. Kindrick (ORCID: https://orcid.org/0000-0003-1519-9721)
- Adam G. Sowalsky (ORCID: https://orcid.org/0000-0003-2760-1853)
- Carleen Klumpp‐Thomas (ORCID: https://orcid.org/0000-0002-6646-6132)
- Michele Ceribelli (ORCID: https://orcid.org/0000-0001-9857-9521)
- Erica L. Beatson (ORCID: https://orcid.org/0000-0003-4517-906X)
- Crystal McKnight (ORCID: https://orcid.org/0009-0007-6554-5772)
- Giulia C. Napoli (ORCID: https://orcid.org/0009-0006-7354-8693)
- Douglas K. Price (ORCID: https://orcid.org/0000-0002-7051-7510)
- William D. Figg (ORCID: https://orcid.org/0000-0003-2428-5613)
- Emily N. Risdon (ORCID: https://orcid.org/0000-0002-5888-8634)
- JuanJuan Yin (ORCID: https://orcid.org/0000-0001-6739-5463)
- Cindy H. Chau (ORCID: https://orcid.org/0000-0002-6928-3833)
- Benjamin C. Brim (ORCID: https://orcid.org/0000-0002-6713-3292)
Institutions
- National Institutes of Health (US)
- National Cancer Institute (US)
- National Center for Advancing Translational Sciences (US)
Publication Details
- Journal
- Cancer Research Communications
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1158/2767-9764.crc-25-0096
- Citations
- 1
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- U.S. Department of Health and Human Services