2. Academic Validation
  3. YM155 Inhibition of Survivin Enhances Carboplatin Efficacy in Metastatic Castration-Resistant Prostate Cancer

YM155 Inhibition of Survivin Enhances Carboplatin Efficacy in Metastatic Castration-Resistant Prostate Cancer

  • Pharmaceuticals (Basel). 2025 Nov 18;18(11):1752. doi: 10.3390/ph18111752.
Vicenç Ruiz de Porras 1,  Martin K Bakht 2,  Maria Fernandez-Saorín 3 4,  Clara Alcon 5,  Luis Palomero 6,  Júlia Francisco-Rodon 3 4,  Mariona Figols 7,  Joan Montero 5 8,  Vincenza Conteduca 9,  Himisha Beltran 2,  Albert Font 3 4 10
Affiliations

Affiliations

  • 1 GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
  • 2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • 3 CARE Program, Germans Trias i Pujol Research Institute (IGTP), Camí de les Escoles, s/n, 08916 Badalona, Spain.
  • 4 Badalona Applied Research Group in Oncology (B-ARGO), Catalan Institute of Oncology, Camí de les Escoles, s/n, 08916 Badalona, Spain.
  • 5 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08007 Barcelona, Spain.
  • 6 Department Llenguatges i Sistemes Informàtics, Institute of New Imaging Technologies, Universitat Jaume I, Av. Sos Baynat s/n, 12071 Castellón de la Plana, Spain.
  • 7 Medical Oncology Department, Althaia Xarxa Assistencial Universitària de Manresa, C/Dr. Joan Soler, 1-3, 08243 Manresa, Spain.
  • 8 Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain.
  • 9 Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
  • 10 Department of Medical Oncology, Catalan Institute of Oncology (ICO), 08907 Badalona, Spain.
PMID: 41304997 DOI: 10.3390/ph18111752
Abstract

Background/Objectives: Metastatic castration-resistant prostate Cancer (mCRPC) remains a major clinical challenge due to its aggressive behavior and resistance to therapy. Survivin, a member of the inhibitor of Apoptosis protein family, is overexpressed in various cancers and associated with poor prognosis. YM155 (Sepantronium bromide) suppresses Survivin expression and has demonstrated antitumor activity in preclinical models. We investigated the association between Survivin expression and clinical outcomes in mCRPC patients and evaluated the antitumor activity of YM155, alone and in combination with carboplatin, in mCRPC cell lines. Methods: Analysis of publicly available RNA-seq datasets from mCRPC patients was performed to assess correlations between Survivin expression and clinical outcomes. Radiographic progression-free survival (rPFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared via log-rank or Fisher's exact tests. In vitro assays were conducted on mCRPC cell lines treated with YM155, carboplatin, or both, to evaluate cell viability, clonogenicity, and Apoptosis. Results: Survivin was significantly overexpressed in mCRPC compared with localized prostate Cancer and was even higher in castration-resistant neuroendocrine disease. High Survivin levels were associated with shorter OS (p = 0.006). In patients treated with platinum-based therapies, high Survivin was also linked to shorter rPFS (p = 0.01), reduced OS (p = 0.006), and a smaller PSA decline (p = 0.006). In vitro, YM155 reduced Survivin expression, impaired cell viability and colony formation, induced Apoptosis, and synergistically enhanced the cytotoxicity of carboplatin. Conclusions: Our findings suggest that Survivin may serve as a prognostic biomarker and potential therapeutic target in platinum-treated, AR-independent mCRPC. The integration of clinical and functional data provides translational support for combining the Survivin Inhibitor YM155 with platinum-based therapy. These results warrant further validation in larger patient cohorts and in vivo models.

Keywords

YM155; carboplatin; metastatic castration-resistant prostate cancer; survivin.

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