Figure 1 from Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7–Expressing CRPC Models
<p>Identification of Synergistic BH<sub>3</sub>-mimetic–based combinations in LNCaP95 and VCaP-CR Cells. <b>A,</b> Correlation plot depicting DBSumNeg (synergy score) for drugs that pair well with S63845 across LNCaP95 and VCaP-CR lines. <b>B,</b> All pairings of BH<sub>3</sub> mimetics ranked by average DBSumNeg across LNCaP95 and VCaP-CR lines. <b>C</b> to <b>F,</b> Example drug screen data from A-1331852 paired with S63845 in VCaP-CR (<b>C</b> and <b>D</b>) and LNCaP95 (<b>E</b> and <b>F</b>) cells using CellTiter-Glo to measure response. Cell viability (<b>C</b> and <b>E</b>) and Bliss synergy were calculated for each point. Z-plots depict Bliss synergy score at each concentration (<b>D</b> and <b>F</b>). <b>G,</b> Patient mRNA sequencing data from the SU2C 2019 cohort of patients with mCRPC reveals the expression of <i>AR</i>, <i>BCL2</i>, <i>Bcl-xL</i>, and <i>MCL1</i>. Cohort expression was displayed utilizing GraphPad Prism 10, and data are expressed as fragments per kilobase of transcript per million mapped reads (FPKM).</p>
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)
Publication Details
- Published
- 2025-08-21
- DOI
- https://doi.org/10.1158/2767-9764.29957567
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00