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Cancers
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Advances and Research Priorities for Metastatic-Hormone-Resistant Prostate Cancer
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Advances and Research Priorities for Metastatic-Hormone-Resistant Prostate Cancer

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

Deadline for manuscript submissions: closed (31 May 2025) | Viewed by 1735

Special Issue Editor

Dr. Bassel Nazha

E-Mail Website
Guest Editor
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA
Interests: prostate cancer; genitourinary cancer; renal cell carcinoma; penile cancer; blad-der cancer; urothelial cancer

Special Issue Information

Dear Colleagues,

This Special Issue will cover the advances and research priorities for metastatic-hormone-resistant prostate cancer. It will include the sequencing of combination therapies, highlighting novel molecular targets such as DDL3 and the emerging use of PARP inhibitors and radiopharmaceuticals as a standard of care treatment options. The Special Issue will also adopt the precision oncology viewpoint and highlight the role of ctDNA for real-time treatment personalization and monitoring. Papers on novel theragnostics and PSMA-targeted therapies are welcome in addition to ones highlighting the role of radiation therapy in hormone-resistant disease. Lastly, the Special Issue will include the need for a clinical trial design that investigates symptom and quality of life (QOL) outcome measures. Additionally, papers focused on understanding the real-world effectiveness and patient-centered benefits of new therapies are welcome.

I look forward to receiving your contributions.

Dr. Bassel Nazha
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
  • combination therapy
  • precision oncology
  • ctDNA
  • radiation therapy

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Published Papers (2 papers)

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Research

31 pages, 4379 KiB  
Article
Stathmin Serine 16 Phosphorylation Is a Key Regulator of Cell Cycle Progression Without Activating Migration and Invasion In Vitro
by Paul L. Deford, Andrew P. VonHandorf, Brian G. Hunt, Simran Venkatraman, Susan E. Waltz, Katherine A. Burns and Susan Kasper
Cancers 2025, 17(14), 2322; https://doi.org/10.3390/cancers17142322 (registering DOI) - 12 Jul 2025
Abstract
Background: Treatment of metastatic cancer remains a challenge, because cancer cells acquire resistance even to the most contemporary therapies. This study analyzed the role of the phosphoprotein Stathmin 1 (STMN1) in regulating cancer cell growth and metastatic potential. Methods: Public datasets [...] Read more.
Background: Treatment of metastatic cancer remains a challenge, because cancer cells acquire resistance even to the most contemporary therapies. This study analyzed the role of the phosphoprotein Stathmin 1 (STMN1) in regulating cancer cell growth and metastatic potential. Methods: Public datasets with metastatic castration-resistant prostate cancer (mCRPC) and breast cancer (BC) were analyzed to determine the interrelationship between STMN1, hepatocyte growth factor (HGF) and MET proto-oncogene (MET) expression, overall survival, and response to chemotherapy. Site-directed mutagenesis, cell cycle analysis, proliferation, and migration and invasion assays determined the impact of STMN1 phosphorylation on proliferation and metastatic potential. Results: Increased STMN1 associates with HGF and MET gene expression in mCRPC, and taxane chemotherapy further increases HGF expression. STMN1 and HGF are highest, and overall survival is poorest in mCRPC in the liver compared to other sites, implying the metastatic site influences their expression levels and potentially the pattern of metastatic spread. Increased STMN1 and MET also predict taxane responsiveness in BC patients. Analysis of STMN1 serine (S)16, 25, 38, and 63 determined that total (t) STMN1 and STMN1 S16 phosphorylation (pSTMN1S16) are co-regulated by HGF/MET during cell cycle progression, pSTMN1S16 alone can promote cell proliferation, and pSTMN1S16 shortens the cell cycle similar to HGF treatment, while STMN1S16 dephosphorylation lengthens the cell cycle to arrest cell growth in G2/M, similar to HGF plus the MET inhibitor AMG337. Importantly, STMN1S16 does not promote metastasis. Conclusions: Selectively inhibiting STMN1S16 phosphorylation may provide an alternative strategy for inhibiting MET-mediated cell growth to eliminate metastatic cancer cells and inhibit further metastasis. Full article
(This article belongs to the Special Issue Advances and Research Priorities for Metastatic-Hormone-Resistant Prostate Cancer)
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18 pages, 2438 KiB  
Article
Cost-Effectiveness of PARP Inhibitors for Patients with BRCA1/2-Positive Metastatic Castration-Resistant Prostate Cancer—The Canadian Perspective
by Ivan Yanev, Armen G. Aprikian, Brendan L. Raizenne and Alice Dragomir
Cancers 2025, 17(1), 40; https://doi.org/10.3390/cancers17010040 - 26 Dec 2024
Viewed by 1432
Abstract
Background/Objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of [...] Read more.
Background/Objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective. Methods: Partitioned survival models were created to represent mCRPC disease after progression until death. Survival inputs for BRCA1/2-mutated patients were extracted from the PROfound, TRITON3, and TALAPRO-1 clinical trials, while Canadian-specific costs are presented in 2023 dollars. Upon progression, patients were treated with chemotherapy. The considered time horizon was 5 years and outcomes were discounted at 1.5% per year. Results: PARP inhibitors provide an additional survival of 0.19 quality-adjusted life years (QALY) when compared to the current standard of care, with additional costs of CAD 101,679 resulting in an incremental cost-utility ratio (ICUR) of CAD 565,383/QALY. The results were most sensitive to PARP inhibitors’ acquisition costs and health-state utilities. PARP inhibitors required price reductions of up to 83% to meet the CAD 50,000/QALY willingness-to-pay threshold (WTP). Conclusions: While providing survival benefits to previously progressed mCRPC patients presenting deleterious BRCA1/2 gene mutations, PARP inhibitors are not cost-effective and require major price reductions to reach local WTP thresholds. Full article
(This article belongs to the Special Issue Advances and Research Priorities for Metastatic-Hormone-Resistant Prostate Cancer)
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