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Advancements in Molecular Research of Prostate Cancer
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Advancements in Molecular Research of Prostate Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 9953

Special Issue Editor

Prof. Dr. Anait S. Levenson

E-Mail Website
Guest Editor
Department of Biomedical Sciences, College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA
Interests: prostate and breast cancers; molecular mechanisms of cancer progression; pre-clinical mouse models; targeted therapies; natural anticancer agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

We are delighted to announce the call for submissions to a Special Issue of Cancers focusing on the topic of "Advancements in Molecular Research of Prostate Cancer." Prostate cancer is a significant health concern worldwide, and understanding its molecular aspects is crucial for improved diagnosis, treatment, and patient outcomes.

This Special Issue aims to provide a comprehensive overview of the latest advancements in molecular research related to prostate cancer. We invite the submission of original research articles and reviews that cover various aspects of prostate cancer molecular biology, including but not limited to the following:

  • Genetic and epigenetic alterations in prostate cancer development and progression.
  • Identification and characterization of prostate cancer biomarkers for early detection and prognosis.
  • Molecular mechanisms underlying therapeutic resistance in prostate cancer.
  • Novel molecular targets and therapeutic strategies for prostate cancer treatment.
  • Genomic and proteomic profiling of prostate cancer to unravel its heterogeneity.
  • Modeling different stages of prostate cancer in genetically engineered mouse models.
  • Identification and characterization of novel molecular targets in prostate cancer.
  • Development and evaluation of targeted therapies for prostate cancer (pre-clinical and clinical studies).

All submitted articles will undergo a rigorous peer review process to ensure the highest scientific quality and relevance to the field. We encourage contributions from researchers, clinicians, and experts in the field of prostate cancer research and oncology.

By consolidating the latest research findings and molecular insights, we aim to advance our understanding of prostate cancer and pave the way for personalized and effective therapeutic approaches. Your valuable contributions to this Special Issue will contribute significantly to the progress in prostate cancer research.

If you have any questions, require further information, or need any assistance, please do not hesitate to contact us. We are here to support and facilitate your participation in this Special Issue.

Thank you for your attention to this matter, and we eagerly anticipate receiving your valuable submissions.

Prof. Dr. Anait S. Levenson
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 communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers is an international peer-reviewed open access semimonthly 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
  • molecular targets
  • tumor heterogeneity
  • targeted interception and therapies
  • noninvasive biomarkers
  • precision oncology

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Published Papers (6 papers)

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Research

Jump to: Review

14 pages, 2043 KB  
Article
Synergistic Efficacy of WST11-VTP and P-Selectin-Targeted Nanotherapy in a Preclinical Prostate Cancer Model
by Lucas Nogueira, Ricardo Alvim, Hanan Baker, Karan Nagar, Jasmine Thomas, Laura Alvim, Kwanghee Kim, Daniel A. Heller, Augusto Reis, Avigdor Scherz and Jonathan Coleman
Cancers 2025, 17(14), 2361; https://doi.org/10.3390/cancers17142361 - 16 Jul 2025
Viewed by 481
Abstract
Objective: Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize [...] Read more.
Objective: Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize side effects, existing vascular-targeted photodynamic therapy (VTP) and nanodrug therapies often face limitations, such as recurrence and insufficient drug concentration at the tumor site. This study investigated a novel approach that combines VTP with systemic treatment using drug-loaded nanoparticles in a murine model, demonstrating substantial advancements beyond current monotherapies. Methods: SCID (severe combined immunodeficiency) mice were engrafted with androgen-sensitive prostate tumor cells (LNCaP-AR) and treated with a combination of VTP and two different drugs linked to fucoidan nanoparticles (Enzalutamide and Paclitaxel). Experiments were performed using different cohorts: the evaluation of oncological effect, the administration time and concentration of systemic therapy, a comparison of efficacy between VTP and radiotherapy, and the induction of the abscopal effect in untreated synchronous tumors. Results: The groups that received combination therapy showed better tumor control. After eight weeks, the recurrence-free survival rates were 87.5%, 62.5%, and 50% in the VTP + N-PAC, VTP + N-ENZ, and VTP monotherapy groups, respectively (p < 0.05). There was a significant difference in the intra-tumoral concentration of nanodrugs between the groups with combined treatment and monotherapy. After two weeks, the monotherapy groups showed almost total elimination of the drugs, whereas in the combined therapy groups, this concentration remained high, starting to decrease after three weeks (p < 0.05). Treatment with nanodrugs associated with VTP showed superior oncological benefits compared to radiotherapy alone or in combination with other therapies. The abscopal effect on synchronous tumors was not demonstrated with VTP alone or in combination with nanodrugs. Conclusions: Combining vascular photodynamic therapy with nanodrugs was highly effective in treating a prostate tumor model, leading to increased survival and a reduced risk of tumor recurrence. This approach significantly advances beyond existing VTP and nanodrug therapies by improving tumor control, ensuring sustained intra-tumoral drug concentration, and yielding superior oncological outcomes. Our results suggest that this therapy is a potential treatment option for prostate tumors treated with VTP in future clinical trials. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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23 pages, 4896 KB  
Article
5-Aminolevulinic Acid: A Novel Approach to Improving Radioresistance in Prostate Cancer
by Fumisato Maesaka, Yasushi Nakai, Takanori Yoshida, Mitsuru Tomizawa, Takuto Shimizu, Takuya Owari, Kenta Onishi, Makito Miyake, Hiroki Kuniyasu, Kiyohide Fujimoto and Nobumichi Tanaka
Cancers 2025, 17(8), 1286; https://doi.org/10.3390/cancers17081286 - 10 Apr 2025
Viewed by 679
Abstract
Background/Objectives: Prostate cancer (PCa) cells may acquire radioresistance during radiation therapy (RT), resulting in PCa recurrence. This study was aimed at investigating the radiosensitizing effect of 5-aminolevulinic acid (5-ALA) on radioresistant PCa cells. Methods: Radioresistant PCa cells were developed through successive [...] Read more.
Background/Objectives: Prostate cancer (PCa) cells may acquire radioresistance during radiation therapy (RT), resulting in PCa recurrence. This study was aimed at investigating the radiosensitizing effect of 5-aminolevulinic acid (5-ALA) on radioresistant PCa cells. Methods: Radioresistant PCa cells were developed through successive irradiation of two human PCa cell lines (PC-3 and DU 145) and a murine PCa cell line (Myc-CaP). The radiosensitivity of these PCa cells and the radiosensitizing effect of 5-ALA were evaluated using clonogenic assays. Mitochondrial accumulation of protoporphyrin IX (PpIX) and mitochondrial reactive oxygen species (ROS) were evaluated. A syngeneic mouse model with radioresistant PCa was established, and the immunohistochemistry of cell specimens from PCa patients with local recurrence after primary RT was examined. Results: Radioresistant PCa cells showed lower radiosensitivity compared to parental PCa cells. In radioresistant PCa cells with 5-ALA administration, compared to the group administered irradiation alone, the survival rate after irradiation was significantly reduced by promoting mitochondria-mediated apoptosis caused by increased PpIX accumulation and mitochondrial ROS generation. Similar results were observed in vivo. However, compared with parental PCa cells, radioresistant PCa cells were less affected by the radiosensitizing effect of 5-ALA, owing to decreased PpIX accumulation and mitochondrial ROS production caused by upregulated expression of the drug transporter ABCG2. ABCG2 expression was upregulated in human PCa specimens with post-RT recurrence. Conclusions: 5-ALA enhanced the antitumor effects of RT in radioresistant PCa cells; however, ABCG2 upregulation decreased PpIX accumulation, resulting in a reduced radiosensitizing effect of 5-ALA on radioresistant PCa cells compared with that on parental PCa cells. ABCG2 could be a potential therapeutic target for overcoming radioresistance. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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13 pages, 2118 KB  
Article
The Role of Local Prostate and Metastasis-Directed Radiotherapy in the Treatment of Oligometastatic Prostate Cancer
by Seo Hee Choi, Seung-Hoon Beom, Young Deuk Choi, Won Sik Ham, Hyunho Han, Woong Kyu Han, Won Sik Jang, Seung Hwan Lee and Jaeho Cho
Cancers 2024, 16(18), 3159; https://doi.org/10.3390/cancers16183159 - 14 Sep 2024
Cited by 1 | Viewed by 1846
Abstract
Background/Objectives: Oligometastatic prostate cancer (OMPC) represents an early stage of metastatic disease characterized by a limited number of lesions. Recent advancements in imaging and treatment have revived interest in personalized therapies, including metastasis-directed radiotherapy (OMDRT) and primary prostate radiotherapy (PPR). This study evaluates [...] Read more.
Background/Objectives: Oligometastatic prostate cancer (OMPC) represents an early stage of metastatic disease characterized by a limited number of lesions. Recent advancements in imaging and treatment have revived interest in personalized therapies, including metastasis-directed radiotherapy (OMDRT) and primary prostate radiotherapy (PPR). This study evaluates the impact of OMDRT timing and the role of PPR on survival outcomes in OMPC patients; Methods: In this retrospective cohort study, 82 patients with OMPC who underwent OMDRT between 2010 and 2019 were analyzed. Patients were classified based on OMDRT timing (early vs. late) and disease type (synchronous vs. metachronous). Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, assessed via Kaplan-Meier analysis and Cox proportional hazards models; Results: Among the patients, 36 (43.9%) had synchronous and 46 (56.1%) had metachronous OMD. With a median follow-up of 32 months, the 5-year PFS and OS rates were 77.5% and 88.5%, respectively. Early OMDRT significantly improved PFS (HR 0.461, 95% CI: 0.257–0.826, p = 0.009) and OS (HR 0.219, 95% CI: 0.080–0.603, p = 0.003). Subgroup analysis showed the most favorable outcomes for synchronous OMD patients receiving early OMDRT, with a median PFS of 22.2 months and a 5-year survival rate of 42.1%. The treatment of the primary prostate provided a survival benefit in the OS of synchronous OMD patients (5-year 83.1% vs. 50%, p = 0.025), and there was a further improvement in OS after PPR (5-year 87.7% vs. 50%, p = 0.015). Conclusions: Early OMDRT significantly enhances survival outcomes in OMPC, in both synchronous and metachronous cases. The integration of PPR can further improve results, emphasizing the importance of early intervention and personalized treatment strategies. To more definitively clarify our findings across various clinical situations, further studies with larger cohorts or prospective designs are necessary. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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12 pages, 1472 KB  
Article
Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer
by Enrique Perez-Navarro, Vincenza Conteduca, Juan M. Funes, Jose I. Dominguez, Miguel Martin-Serrano, Paolo Cremaschi, Maria Piedad Fernandez-Perez, Teresa Alonso Gordoa, Albert Font, Sergio Vázquez-Estévez, Aránzazu González-del-Alba, Daniel Wetterskog, Begona Mellado, Ovidio Fernandez-Calvo, María José Méndez-Vidal, Miguel Angel Climent, Ignacio Duran, Enrique Gallardo, Angel Rodriguez Sanchez, Carmen Santander, Maria Isabel Sáez, Javier Puente, Julian Tudela, Cecilia Marinas, María Jose López-Andreo, Daniel Castellano, Gerhardt Attard, Enrique Grande, Antonio Rosino, Juan A. Botia, Jose Palma-Mendez, Ugo De Giorgi and Enrique Gonzalez-Billalabeitiaadd Show full author list remove Hide full author list
Cancers 2024, 16(14), 2535; https://doi.org/10.3390/cancers16142535 - 14 Jul 2024
Cited by 1 | Viewed by 2102
Abstract
The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. [...] Read more.
The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan–Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11–3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11–3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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Review

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29 pages, 1939 KB  
Review
Peroxisomal Alterations in Prostate Cancer: Metabolic Shifts and Clinical Relevance
by Mohamed A. F. Hussein, Celien Lismont, Hongli Li, Ruizhi Chai, Frank Claessens and Marc Fransen
Cancers 2025, 17(13), 2243; https://doi.org/10.3390/cancers17132243 - 4 Jul 2025
Viewed by 1035
Abstract
Cancer is hallmarked by uncontrolled cell proliferation and enhanced cell survival, driven by a complex interplay of factors—including genetic and epigenetic changes—that disrupt metabolic and signaling pathways and impair organelle function. While the roles of mitochondria and the endoplasmic reticulum in cancer are [...] Read more.
Cancer is hallmarked by uncontrolled cell proliferation and enhanced cell survival, driven by a complex interplay of factors—including genetic and epigenetic changes—that disrupt metabolic and signaling pathways and impair organelle function. While the roles of mitochondria and the endoplasmic reticulum in cancer are widely recognized, emerging research is now drawing attention to the involvement of peroxisomes in tumor biology. Peroxisomes are essential for lipid metabolism, including fatty acid α- and β-oxidation, the synthesis of docosahexaenoic acid, bile acids, and ether lipids, as well as maintaining redox balance. Despite their critical functions, the role of peroxisomes in oncogenesis remains inadequately explored. Prostate cancer (PCa), the second most common cancer in men worldwide, exhibits a unique metabolic profile compared to other solid tumors. In contrast to the glycolysis-driven Warburg effect, primary PCa relies primarily on lipogenesis and oxidative phosphorylation. Peroxisomes are intricately involved in the metabolic adaptations of PCa, influencing both disease progression and therapy resistance. Key alterations in peroxisomal activity in PCa include the increased oxidation of branched-chain fatty acids, upregulation of α-methylacyl coenzyme A racemase (a prominent PCa biomarker), and downregulation of 1-alkyl-glycerone-3-phosphate synthase and catalase. This review critically examines the role of peroxisomes in PCa metabolism, progression, and therapeutic response, exploring their potential as biomarkers and targets for therapy. We also consider their relationship with androgen receptor signaling. A deeper understanding of peroxisome biology in PCa could pave the way for new therapies to improve patient outcomes. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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31 pages, 3173 KB  
Review
Immunotherapy in Prostate Cancer: From a “Cold” Tumor to a “Hot” Prospect
by Whi-An Kwon and Jae Young Joung
Cancers 2025, 17(7), 1064; https://doi.org/10.3390/cancers17071064 - 21 Mar 2025
Cited by 4 | Viewed by 2896
Abstract
Immunotherapy has shown limited efficacy in prostate cancer, largely due to low tumor immunogenicity, sparse tumor-infiltrating lymphocytes, and a suppressive microenvironment. Recent therapeutic strategies aim to boost immune responses and counteract immunosuppressive factors through interventions such as immune checkpoint inhibitors, immunogenic cell death-inducing [...] Read more.
Immunotherapy has shown limited efficacy in prostate cancer, largely due to low tumor immunogenicity, sparse tumor-infiltrating lymphocytes, and a suppressive microenvironment. Recent therapeutic strategies aim to boost immune responses and counteract immunosuppressive factors through interventions such as immune checkpoint inhibitors, immunogenic cell death-inducing therapies, and the targeted blockade of pathways like that of transforming growth factor-β. Vaccine-based approaches, potent immune adjuvants, and engineered chimeric antigen receptor (CAR) T cells are also being investigated to overcome local immune inhibitory signals. Advancements in imaging, multi-omic profiling, and liquid biopsies offer promising avenues for real-time monitoring, better patient selection, and precision treatment. This review provides an overview of the key immunosuppressive features of prostate cancer, current immunotherapeutic modalities, and emerging strategies to transform “cold” tumors into more responsive “hot” targets. By integrating these approaches, we may achieve more durable clinical benefits for patients with advanced or metastatic prostate cancer. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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