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Castration- and Therapy-Resistant Prostate Cancer: Biomarkers, Therapeutic Targets, and Emerging Approaches

A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 30 December 2026 | Viewed by 752

Editor


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Guest Editor
Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy
Interests: castration-resistant prostate cancer (CRPC); extracellular vesicles; sex steroid hormones in cancers (breast, prostate, pancreatic and colon); triple negative breast cancer; sex steroid receptors; growth factor receptors signaling
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Special Issue Information

Dear Colleagues,

Although mortality from prostate cancer has decreased over recent decades, it remains the most frequently diagnosed malignancy among men worldwide. The major clinical challenge arises when prostate cancer progresses to a castration-resistant and aggressive form (CRPC), for which therapeutic options remain limited and largely non-curative.

In CRPC, androgen receptor (AR) signaling often persists despite androgen deprivation and continues to drive tumor progression. In addition to AR, multiple molecular players and alternative signaling pathways can cooperate with or bypass AR activity to sustain disease advancement. Several pathways, including EGFR-related signaling, have been shown to contribute to CRPC progression both in the presence and absence of AR expression.

To date, the identification of reliable biomarkers and actionable therapeutic targets represents a major priority for improving disease stratification, understanding resistance mechanisms, and developing innovative treatment strategies for this aggressive cancer subtype.

This Special Issue aims to provide an updated and comprehensive overview of recent advances in castration-resistant prostate cancer, encompassing the discovery of novel biomarkers, therapeutic targets, and emerging approaches for disease management. The Special Issue welcomes the contributions of original research articles and reviews addressing molecular mechanisms, signal transduction pathways, translational research, preclinical studies, and clinical perspectives.

Dr. Pia Giovannelli
Guest Editor

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Keywords

  • castration-resistant prostate cancer
  • therapy-resistant prostate cancer
  • androgen receptor signaling
  • EGFR-related signaling
  • biomarkers
  • drug resistance
  • signal transduction pathways
  • translational research
  • targeted therapy

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Published Papers (1 paper)

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Research

21 pages, 11433 KB  
Article
Real-World Outcomes of DNA Damage Repair Altered Metastatic Castration-Resistant Prostate Cancer: Insights from FFPE-Based Genomic Profiling
by Eleonora Lai, Francesco Pierantoni, Ilaria Zampiva, Davide Bimbatti, Melissa Ballestrin, Greta Pretto, Anna Milani, Elisa Erbetta, Salim Jubran, Chiara Pittarello, Andrea Di Marco, Nicolò Cavasin, Carolina Zamuner, Aichi Msaki, Lidia Moserle, Matteo Curtarello, Elisa Boldrin, Marco Montagna, Veronica Varano, Vasileios Mourmouras, Ivana Cataldo, Francesco Claps, Antonio Amodeo, Silvia Stragliotto, Marco Maruzzo and Umberto Bassoadd Show full author list remove Hide full author list
Cancers 2026, 18(15), 2400; https://doi.org/10.3390/cancers18152400 - 25 Jul 2026
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Abstract
Background: Germline and somatic variants in DNA Damage Repair (DDR) genes are found in approximately one-fourth of patients with metastatic prostate cancer (PC). However, their precise prognostic role and predictive impact on standard therapies remain controversial. Methods: This retrospective, single-center study evaluated the [...] Read more.
Background: Germline and somatic variants in DNA Damage Repair (DDR) genes are found in approximately one-fourth of patients with metastatic prostate cancer (PC). However, their precise prognostic role and predictive impact on standard therapies remain controversial. Methods: This retrospective, single-center study evaluated the prevalence of germline/somatic DDR aberrations in 287 eligible patients with metastatic prostate cancer (mPC), treated between 2017 and 2022. Clinical characteristics and treatment outcomes (PFS and OS) for chemotherapy (taxanes) or next-generation hormonal therapies (NHT) were compared between DDR-mutated (DDRmut) and wild-type (DDRwt) cohorts. Results: Sixty-three patients (21.9%) were DDRmut, with BRCA2 (12.5%), ATM (3.1%), and BRCA1 (1.39%) being the most common alterations. A family history of breast, ovarian, or prostate cancer strongly predicted DDRmut status (47.0% vs. 14.0%, p = 0.0001). Tissue samples remained evaluable for sequencing up to 180 months from collection. Overall baseline characteristics were similar between cohorts, and BRCA1/2- and ATM-mutated patients treated with first-line taxanes for mCRPC presented with non significantly highermedian OS compared to DDRwt patients (70 vs. 36 months; p = 0.30). On the contrary, the DDRmut subgroup showed a trend toward shorter PFS (12 vs. 18 months; p = 0.04) when treated with first-line NHT. No significant differences were observed with third-line Cabazitaxel. Conclusions: Formalin-fixed paraffin-embedded (FFPE) prostate tissue is highly reliable for DDR, possibly integrating novel liquid biopsy approaches for DDR evaluation. In a real-world setting, BRCA1/2 and ATM variants identify a distinct molecular subgroup that derives preferential survival benefit from first-line taxanes over standard hormonal intensification. Full article
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