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Pharmaceuticals
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Advances in Prostate Cancer Therapeutics
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Advances in Prostate Cancer Therapeutics

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 March 2026 | Viewed by 8144

Special Issue Editor

Dr. David Danielpour

E-Mail Website
Guest Editor
Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA
Interests: function and regulation of TGF-beta expression and signaling in prostate and renal cancers; androgen receptor signaling; cross-talk of TGF-beta with IGF-I, AKT, mTOR, androgen receptor, and Hic-5; survivin in cancer; Notch/Jagged1 signaling; drug discovery; YM155; mTOR inhibitors; TGF-beta signaling inhibitors; apoptosis; hypoxia and hypoxia-inducible pathways; AMPKs; chemoprevention; polyphenols
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer (PCa), the second most frequently diagnosed malignancy in men, is a leading cause of cancer mortality worldwide. Although localized PCa is often managed effectively with surgery and radiation therapy, metastatic PCa presents significant therapeutic challenges. Androgen deprivation therapy (ADT) remains the cornerstone of treatment; nonetheless, resistance frequently develops, leading to castration-resistant PCa (CRPC). The past decade has seen remarkable advancement in therapeutic strategies, including next-generation androgen receptor signaling inhibitors, poly(ADP-ribose) polymerase (PARP) inhibitors, radiotherapies, immunotherapies, and combination regimens. Despite such progress, treatment resistance, biomarker-driven patient selection, and the optimal sequencing of therapies remain critical areas of ongoing research.

This Special Issue of Pharmaceuticals seeks to highlight the latest developments in PCa therapeutics, with a focus on novel drug discovery, mechanisms of resistance, biomarkers for treatment response, and personalized medicine approaches. We invite original articles, reviews, and preclinical and clinical studies that explore cutting-edge treatment strategies, translational research, and emerging therapeutic modalities aimed at improving patient outcomes.

Researchers, clinicians, and industry experts are encouraged to submit their work to this Special Issue. For further details, please visit www.mdpi.com.

Dr. David Danielpour
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • androgen deprivation therapy (ADT)
  • castration-resistant prostate cancer (CRPC)
  • androgen receptor signaling inhibitors
  • PARP inhibitors
  • ionizing radiation therapy
  • radiopharmaceuticals
  • immunotherapy
  • biomarkers
  • personalized medicine
  • therapeutic resistance
  • targeted therapy
  • combination therapy
  • hormone-sensitive prostate cancer (HSPC)
  • next-generation therapeutics
  • translational oncology

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Published Papers (4 papers)

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Research

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16 pages, 2574 KB  
Article
YM155 Inhibition of Survivin Enhances Carboplatin Efficacy in Metastatic Castration-Resistant Prostate Cancer
by Vicenç Ruiz de Porras, Martin K. Bakht, Maria Fernandez-Saorín, Clara Alcon, Luis Palomero, Júlia Francisco-Rodon, Mariona Figols, Joan Montero, Vincenza Conteduca, Himisha Beltran and Albert Font
Pharmaceuticals 2025, 18(11), 1752; https://doi.org/10.3390/ph18111752 - 18 Nov 2025
Viewed by 706
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Prostate Cancer Therapeutics)
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Review

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17 pages, 1277 KB  
Review
Recent Advances in Androgen Receptor Pathway Inhibitors for Castration-Sensitive Prostate Cancer
by Andrea Lancia, Marco Oderda, Federico Camilli, Eleonora Festa, Marta Bottero, Emanuele Alì, Salvatore La Mattina, Elisabetta Bonzano, Jessica Saddi, Beatrice Detti, David Alberto Santos Hernandez and Gianluca Ingrosso
Pharmaceuticals 2025, 18(11), 1697; https://doi.org/10.3390/ph18111697 - 8 Nov 2025
Viewed by 2590
Abstract
Prostate cancer (PCa) is the second most common cancer in men, and it is frequently diagnosed at an advanced stage of the disease. Androgen Deprivation Therapy (ADT) has traditionally represented the backbone of therapy for high-risk, recurrent, and metastatic disease; however, in the [...] Read more.
Prostate cancer (PCa) is the second most common cancer in men, and it is frequently diagnosed at an advanced stage of the disease. Androgen Deprivation Therapy (ADT) has traditionally represented the backbone of therapy for high-risk, recurrent, and metastatic disease; however, in the last ten years a new group of molecules known as androgen receptor pathway inhibitors (ARPIs) have been demonstrated to improve outcomes in metastatic patients when added to ADT. Developed and validated originally in the setting of castration-resistant disease, ARPIs have been implemented progressively earlier in the natural history of PCa, involving patients who have never received ADT before or that are still responsive to this treatment. Considering the strong evidence for treatment intensification in patients with high-risk features, with this review we aim to provide a complete overview of the current indications for the use of ARPIs through all the stages of castration-sensitive prostate cancer (CSPC). Full article
(This article belongs to the Special Issue Advances in Prostate Cancer Therapeutics)
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Other

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19 pages, 1875 KB  
Systematic Review
PARP Inhibitors for Metastatic CRPC: More Answers than Questions, a Systematic Review and Meta-Analysis
by Ray Manneh, Javier Molina-Cerrillo, Guillermo de Velasco, Linda Ibatá, Susan Martínez, Álvaro Ruiz-Granados and Teresa Alonso-Gordoa
Pharmaceuticals 2025, 18(7), 1015; https://doi.org/10.3390/ph18071015 - 8 Jul 2025
Viewed by 2112
Abstract
PARP inhibitors (PARPi), alone or in combination with androgen receptor signaling inhibitors (ARSi), have shown clinical benefit in metastatic castration-resistant prostate cancer (mCRPC), particularly in tumors with homologous recombination repair (HRR) gene alterations. Recent data from the TALAPRO-2 trial complete the current evidence [...] Read more.
PARP inhibitors (PARPi), alone or in combination with androgen receptor signaling inhibitors (ARSi), have shown clinical benefit in metastatic castration-resistant prostate cancer (mCRPC), particularly in tumors with homologous recombination repair (HRR) gene alterations. Recent data from the TALAPRO-2 trial complete the current evidence on PARPi–ARSi combination strategies in this setting. Background/Objectives: To evaluate the efficacy and safety of PARPi-based therapies—monotherapy and combination with ARSi—in patients with mCRPC, focusing on molecular subgroups defined by DNA repair alterations. Methods: We conducted a systematic review and meta-analysis of phase III randomized controlled trials (RCTs) assessing PARPi as monotherapy or in combination with ARSi. Searches were performed in PubMed, EMBASE, the Cochrane Library, and oncology conference proceedings up to February 2025. Outcomes included radiographic progression-free survival (rPFS), overall survival (OS), second progression-free survival (PFS2), and grade ≥3 adverse events (AEs). Data were pooled using a random-effects model, with subgroup analyses by DNA repair status. Results: Five RCTs (n = 2921) were I confirmincluded: three on combination therapy (n = 2271) and two on monotherapy (n = 650). Combination therapy improved rPFS in the ITT (HR = 0.64; 95% CI: 0.56–0.74), HRRm (HR = 0.55; 95% CI: 0.44–0.68), and BRCAm (HR = 0.33; 95% CI: 0.18–0.58) subgroups. OS was also improved in the ITT (HR = 0.80; 95% CI: 0.70–0.92), HRRm (HR = 0.68; 95% CI: 0.55–0.83), and BRCAm (HR = 0.54; 95% CI: 0.34–0.85) groups. No benefit was observed in non-HRRm patients. PFS2 favored combination therapy (HR = 0.77; 95% CI: 0.64–0.91). Grade ≥3 AEs were more frequent (RR = 1.44; 95% CI: 1.20–1.73). Monotherapy improved rPFS in ITT (HR = 0.46; 95% CI: 0.20–0.81) and BRCAm (HR = 0.33; 95% CI: 0.15–0.75); OS benefit was seen only in BRCAm (HR = 0.73; 95% CI: 0.57–0.95). Conclusions: PARPi therapies improve outcomes mainly in HRR- and BRCA-mutated mCRPC. Molecular selection is key to optimizing benefit and minimizing toxicity. Further research on the activity of PARPi combinations in non-HRR mutated mCRPC is needed to better understand the underlying mechanisms of efficacy. Full article
(This article belongs to the Special Issue Advances in Prostate Cancer Therapeutics)
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12 pages, 560 KB  
Systematic Review
Safety and Efficacy of Reduced Dose of Enzalutamide in Patients with Castration-Resistant Prostate Cancer: A Systematic Review
by Zineddine Belabaci, Lucas Mose, Omar El-Taji, Zina Otmani, Zein Alabdin Hannouneh, Issa Mohamad, Thomas Zilli, Osama Mohamad, Nadeem Pervez, Waleed Arafat, Ursula Vogl and Mohamed Shelan
Pharmaceuticals 2025, 18(5), 732; https://doi.org/10.3390/ph18050732 - 16 May 2025
Cited by 1 | Viewed by 2289
Abstract
Objective: To review the efficacy and safety of reduced dose compared to standard dose Enzalutamide treatment for patients with castration-resistant prostate cancer (CRPC). Methods: PubMed, Scopus, Web of Science, and Cochrane databases were searched for randomized controlled trials and cohort studies reporting the [...] Read more.
Objective: To review the efficacy and safety of reduced dose compared to standard dose Enzalutamide treatment for patients with castration-resistant prostate cancer (CRPC). Methods: PubMed, Scopus, Web of Science, and Cochrane databases were searched for randomized controlled trials and cohort studies reporting the use of Enzalutamide in reduced and standard doses in patients with castration-resistant prostate cancer. Searches were limited to articles published in the English language. Outcome assessments included progression-free survival (PFS), overall survival (OS), adverse events, and serum prostate-specific antigen (PSA) response. Results: Ten studies met the inclusion criteria, including 2481 patients treated with Enzalutamide. Seven studies were retrospective cohorts, two were prospective trials, and one was a prospective cohort. No consistent relationship was identified between OS and PFS and the Enzalutamide dosage. Reduced doses of Enzalutamide decreased the incidence of adverse events, particularly among elderly patients. Conclusions: This systematic review suggests that reduced doses of Enzalutamide in CRPC may maintain therapeutic efficacy in selected patients while improving tolerability. However, inconsistent findings and methodological limitations highlight the need for prospective randomized trials to define optimal and individualized dosing strategies. Full article
(This article belongs to the Special Issue Advances in Prostate Cancer Therapeutics)
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