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Prostate Cancer Targeted Therapy: Highlighting Advances in Precision Medicine and...
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Prostate Cancer Targeted Therapy: Highlighting Advances in Precision Medicine and Rational Combination Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 2752

Special Issue Editor

Dr. Alan P. Lombard

E-Mail Website
Guest Editor
1. Department of Urologic Surgery, University of California Davis, Sacramento, CA 95817, USA
2. Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95616, USA
Interests: prostate cancer; AR pathway inhibition; PARP inhibitors; therapeutic response and resistance; drug-tolerant persister cancer cells

Special Issue Information

Dear Colleagues,

The clinical landscape for advanced prostate cancer is rapidly changing. The field is quickly moving toward a targeted paradigm, where individualized patient tumor characteristics will guide treatment decisions, leading to tailored, improved outcomes. Current progress toward the promise of precision medicine for prostate cancer includes PARP inhibitor use for the treatment of tumors with DNA repair defects, pembrolizumab (PD-1 inhibitor) for MMR defective tumors, and the recent approval of 177Lu-PSMA-617 (Pluvicto) for PSMA-positive mCRPC. Rational combinations of new and available therapies are also improving patient management. Notably, our evolving understanding of AR pathway inhibitors and PARP inhibition has led to the approval of combinations of these agents. As our understanding of prostate cancer molecular characteristics, use of biomarkers for patient stratification, and drug synergies improves, new approaches are expected to continue to revolutionize how we treat this disease. In this Special Issue, we seek to highlight cutting-edge research advances working to promote and incorporate the use of targeted and rational approaches for advanced and intractable prostate cancer. Studies detailing basic, translational, and clinical work to advance targeted and rational combination strategies are highly encouraged. Work to develop, understand, and incorporate clinical biomarkers to better stratify patients for treatment are also welcomed. Additionally, reviews summarizing different aspects of targeted therapy for prostate cancer and current clinical findings and perspectives will be warmly accepted for review. We express our warmest thanks for considering this opportunity to highlight the latest research in treating advanced prostate cancer.

Dr. Alan P. Lombard
Guest Editor

Manuscript Submission Information

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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. Biomedicines 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 2600 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
  • precision medicine
  • targeted therapeutics
  • rational drug combinations
  • clinical biomarkers

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Published Papers (2 papers)

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Research

19 pages, 3069 KB  
Article
Cyclophilin Inhibitor Rencofilstat Combined with Proteasome Inhibitor Ixazomib Increases Proteotoxic Cell Death in Advanced Prostate Cancer Cells with Minimal Effects on Non-Cancer Cells
by Carlos Perez-Stable, Alicia de las Pozas, Medhi Wangpaichitr, Robert T. Foster and Daren R. Ure
Biomedicines 2025, 13(10), 2442; https://doi.org/10.3390/biomedicines13102442 - 7 Oct 2025
Viewed by 484
Abstract
Background/Objective: Proteotoxic stress induced by inhibitors of the ubiquitin–proteasome system has been successful in multiple myeloma but not in solid cancers such as prostate cancer. Our objective is to find a combination with proteasome inhibitors that increases apoptotic cell death in all types [...] Read more.
Background/Objective: Proteotoxic stress induced by inhibitors of the ubiquitin–proteasome system has been successful in multiple myeloma but not in solid cancers such as prostate cancer. Our objective is to find a combination with proteasome inhibitors that increases apoptotic cell death in all types of prostate cancer without harming non-cancer cells. Methods: The effectiveness of rencofilstat, a pan-cyclophilin inhibitor, combined with the ixazomib proteasome inhibitor, was investigated in multiple prostate cancer and non-cancer cells. Inducible knockdown of stress response XBP1s and cyclophilins A/B and inducible expression of XBP1s and cyclophilin B were developed in prostate cancer to determine functional roles. Results: Rencofilstat + ixazomib increased apoptotic cell death in prostate cancer but not in non-cancer cells. We investigated the effects on XBP1s and PERK, important unfolded protein response factors required for cells to survive proteotoxic stress. The results revealed that XBP1s had a pro-survival role early, but maintenance at later times of rencofilstat + ixazomib treatment resulted in cell death. In addition, decreased PERK and phospho-eIF2α likely maintained protein synthesis to further enhance proteotoxic stress. In contrast, rencofilstat + ixazomib did not alter XBP1s or PERK in non-cancer cells. Additional genetic experiments showed that the RCF targets cyclophilins A, B, and D had protective effects. Rencofilstat increased extracellular secretion of cyclophilin B, but rencofilstat + ixazomib reduced glycosylation and, likely, the biological function of CD147 (CypB receptor) and decreased downstream ERK signaling. Conclusions: Rencofilstat + ixazomib may be a new strategy for increasing proteotoxic stress and apoptotic cell death in advanced prostate cancer cells with less toxic side effects. Full article
(This article belongs to the Special Issue Prostate Cancer Targeted Therapy: Highlighting Advances in Precision Medicine and Rational Combination Approaches)
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15 pages, 1195 KB  
Article
Long-Term Outcomes After High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy in Very High-Risk Prostate Cancer: A 24-Year Follow-Up
by Pedro J. Prada Gómez, Ana L. Rivero Pérez, Joaquín Carballido Rodríguez, Javier Anchuelo Latorre, Rosa Fabregat Borrás, Marina Gutiérrez Ruiz, Cristina Rodríguez-Acosta Caballero, Carlos F. Carrascal Gordillo, Maria P. Galdós Barroso and Paola A. Navarrete Solano
Biomedicines 2025, 13(6), 1310; https://doi.org/10.3390/biomedicines13061310 - 27 May 2025
Cited by 1 | Viewed by 1819
Abstract
Purpose: To evaluate the long-term oncological outcomes and toxicity profile based on 24 years of follow-up in patients with localized very high-risk prostate cancer (VHR PCa) treated with a combination of high-dose-rate brachytherapy (HDR-BT) and pelvic external beam radiation therapy (EBRT). Methods [...] Read more.
Purpose: To evaluate the long-term oncological outcomes and toxicity profile based on 24 years of follow-up in patients with localized very high-risk prostate cancer (VHR PCa) treated with a combination of high-dose-rate brachytherapy (HDR-BT) and pelvic external beam radiation therapy (EBRT). Methods: A retrospective analysis was conducted on 87 patients with VHR PCa, classified according to National Comprehensive Cancer Network (NCCN) criteria, who received HDR-BT and EBRT. Androgen deprivation therapy (ADT) was administered to 72 patients (82.8%). The primary endpoints were biochemical control and cancer-specific survival (CSS), while the secondary endpoints included local control rates, tumor-free survival (TFS), overall survival (OS), and treatment-related toxicity. Results: The 24-year biochemical control rate was 68% (standard deviation [SD]: ±4%), while CSS and TFS at 24 years were 82% (SD ±4%) and 78% (SD ±4%), respectively. Local control rates remained at 98% at 24 years. Furthermore, the OS rate at 24 years was 30%. Multivariate Cox regression analysis identified the T category in the TNM classification as the only factor significantly associated with biochemical control, with 24-year rates of 69%, 71%, and 50% for patients with T-classifications of ≤T2c, T3a, and T3b-T4, respectively (p = 0.024). Notably, no grade ≥3 late toxicities were observed during the follow-up period. Conclusions: The 24-year outcomes support the viability and therapeutic efficacy of EBRT combined with a conformal HDR-BT boost for patients with VHR PCa. Full article
(This article belongs to the Special Issue Prostate Cancer Targeted Therapy: Highlighting Advances in Precision Medicine and Rational Combination Approaches)
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