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Article ; Online: Talazoparib: a new biomarker-directed therapy in advanced prostate cancer.

Conteduca, Vincenza / De Giorgi, Ugo

2021 Volume 22, Issue 9, Page(s) 1203–1204

MeSH term(s)	Biomarkers ; Humans ; Male ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors ; Prostatic Neoplasms/drug therapy
Chemical Substances	Biomarkers ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors ; talazoparib (9QHX048FRV)
Language	English
Publishing date	2021-08-10
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(21)00450-2
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The 5-WS of targeting DNA-damage repair (DDR) pathways in prostate cancer.

Guida, Annalisa / Mosillo, Claudia / Mammone, Giulia / Caserta, Claudia / Sirgiovanni, Grazia / Conteduca, Vincenza / Bracarda, Sergio

Cancer treatment reviews

2024 Volume 128, Page(s) 102766

Abstract: DNA-damage repair (DDR) pathways alterations, a growing area of interest in oncology, are detected in about 20% of patient with prostate cancer and are associated with improved sensitivity to poly(ADP ribose) polymerases (PARP) inhibitors. In May 2020, ... ...

Abstract	DNA-damage repair (DDR) pathways alterations, a growing area of interest in oncology, are detected in about 20% of patient with prostate cancer and are associated with improved sensitivity to poly(ADP ribose) polymerases (PARP) inhibitors. In May 2020, the Food and Drug Administration (FDA) approved two PARP inhibitors (olaparib and rucaparib) for prostate cancer treatment. Moreover, germline aberrations in DDR pathways genes have also been related to familial or hereditary prostate cancer, requiring tailored health-care programs. These emerging scenarios are rapidly changing diagnostic, prognostic and therapeutic approaches in prostate cancer management. The aim of this review is to highlight the five W-points of DDR pathways in prostate cancer: why targeting DDR pathways in prostate cancer; what we should test for genomic profiling in prostate cancer; "where" testing genetic assessment in prostate cancer (germline or somatic, solid or liquid biopsy); when genetic testing is appropriate in prostate cancer; who could get benefit from PARP inhibitors; how improve patients outcome with combinations strategies.
Language	English
Publishing date	2024-05-17
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	125102-8
ISSN	1532-1967 ; 0305-7372
ISSN (online)	1532-1967
ISSN	0305-7372
DOI	10.1016/j.ctrv.2024.102766
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Zs.A 1022: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Immunogenomic profiles associated with response to life-prolonging agents in prostate cancer.

Conteduca, Vincenza / Brighi, Nicole / Schepisi, Giuseppe / De Giorgi, Ugo

British journal of cancer

2023 Volume 129, Issue 7, Page(s) 1050–1060

Abstract: Prostate cancer is the most commonly diagnosed cancer but the management of advanced prostate cancer remains a therapeutic challenge, despite the survival benefits imparted by several therapeutic discoveries targeting different molecular pathways. The ... ...

Abstract	Prostate cancer is the most commonly diagnosed cancer but the management of advanced prostate cancer remains a therapeutic challenge, despite the survival benefits imparted by several therapeutic discoveries targeting different molecular pathways. The mechanisms of resistance to androgen deprivation and tumour progression to lethal metastatic variants are often regulated by androgen receptor (AR) bypass mechanisms and/or neuroendocrine differentiation. Moreover, recent data also suggested the involvement of adaptive and innate infiltrated immune cells in prostate tumour progression. Improvements in cancer genome analyses contributed to a better understanding of antitumour immunity and provided solutions for targeting highly cancer-specific neoantigens generated from somatic mutations in individual patients. In this review, we investigated the current knowledge on the interplay between cancer development and the complex mechanisms of immune regulation. Particularly, we focused on the role of tumour immune microenvironment, generally characterised by strong barriers for immunotherapy, and we discuss the rationale for the potential application of single agent and combination immune-targeting strategies that could lead to improved outcomes. Careful selection based on clinical and genomic factors may allow identification of patients who could benefit from this treatment approach in multiple settings (from localised to advanced prostate tumour) and in different histological subtypes (from adenocarcinoma to neuroendocrine prostate cancer).
MeSH term(s)	Male ; Humans ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Androgen Antagonists/therapeutic use ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Tumor Microenvironment/genetics
Chemical Substances	Androgen Antagonists ; Receptors, Androgen
Language	English
Publishing date	2023-07-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02354-3
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Article ; Online: Circulating myeloid-derived suppressor cells and survival in prostate cancer patients: systematic review and meta-analysis.

Bronte, Giuseppe / Conteduca, Vincenza / Landriscina, Matteo / Procopio, Antonio Domenico

Prostate cancer and prostatic diseases

2022 Volume 26, Issue 1, Page(s) 41–46

Abstract: Background: Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its efficacy. Some preclinical studies explored the role of MDSCs in prostate ... ...

Abstract	Background: Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its efficacy. Some preclinical studies explored the role of MDSCs in prostate cancer development. We aimed to verify the availability of studies exploring the prognostic effect of circulating MDSCs in prostate cancer patients. Methods: We systematically selected studies for a meta-analysis, which compares survival between prostate cancer patients with high vs low circulating MDSC levels. We extracted or calculated hazard ratios (HRs) and relative 95% confidence intervals (CIs) in terms of overall survival (OS) from selected studies. We calculated the pooled HR and relative 95% CIs and estimated publication bias. Results: Among 133 studies retrieved from search on Pubmed, 5 eligible studies (236 prostate cancer patients) met inclusion criteria. High circulating MDSC levels are associated with a worse OS (HR = 2.19; 95%CI = 1.51-3.17). Heterogeneity was not significant (I Conclusions: High levels of circulating MDSCs induce a worse OS in prostate cancer patients than in those with low levels. This finding supports the importance of MDSC detection and targeting also in prostate cancer patients.
MeSH term(s)	Male ; Humans ; Prostatic Neoplasms/pathology ; Myeloid-Derived Suppressor Cells/pathology ; Prognosis ; Immunotherapy ; Tumor Microenvironment
Language	English
Publishing date	2022-11-21
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	1419277-9
ISSN	1476-5608 ; 1365-7852
ISSN (online)	1476-5608
ISSN	1365-7852
DOI	10.1038/s41391-022-00615-5
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Zs.A 5277: Show issues

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Article ; Online: Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis.

Maiorano, Brigida Anna / De Giorgi, Ugo / Verzoni, Elena / Maiello, Evaristo / Procopio, Giuseppe / Conteduca, Vincenza / Di Maio, Massimo

Targeted oncology

2023 Volume 19, Issue 1, Page(s) 1–11

Abstract: Background: PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically ... ...

Abstract	Background: PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations. Objective: We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC. Patients and methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs). Results: Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected. Conclusions: In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC.
MeSH term(s)	Male ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/adverse effects ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Anemia/drug therapy ; Anemia/epidemiology ; Mutation ; Neutropenia ; Thrombocytopenia/drug therapy ; Thrombocytopenia/epidemiology
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2023-11-22
Publishing country	France
Document type	Meta-Analysis ; Systematic Review
ZDB-ID	2222136-0
ISSN	1776-260X ; 1776-2596
ISSN (online)	1776-260X
ISSN	1776-2596
DOI	10.1007/s11523-023-01016-x
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Article ; Online: Correction to: Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis.

Maiorano, Brigida Anna / De Giorgi, Ugo / Verzoni, Elena / Maiello, Evaristo / Procopio, Giuseppe / Conteduca, Vincenza / Di Maio, Massimo

Targeted oncology

2023 Volume 19, Issue 1, Page(s) 127

Language	English
Publishing date	2023-12-30
Publishing country	France
Document type	Published Erratum
ZDB-ID	2222136-0
ISSN	1776-260X ; 1776-2596
ISSN (online)	1776-260X
ISSN	1776-2596
DOI	10.1007/s11523-023-01025-w
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Article ; Online: Personalized medicine for metastatic prostate cancer: The paradigm of PARP inhibitors.

Maiorano, Brigida Anna / Conteduca, Vincenza / Catalano, Martina / Antonuzzo, Lorenzo / Maiello, Evaristo / De Giorgi, Ugo / Roviello, Giandomenico

Critical reviews in oncology/hematology

2023 Volume 192, Page(s) 104157

Abstract: Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in this field, which definitively enters the era of precision medicine, as mPCa is often ... ...

Abstract	Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in this field, which definitively enters the era of precision medicine, as mPCa is often enriched for defects of homologous recombination repair genes. PARPis are now used as single agents for patients with metastatic castration-resistant PCa. Moreover, combinations of PARPis plus androgen-receptor targeted agents and immune checkpoint inhibitors, and earlier applications of PARPis in the metastatic hormone-sensitive PCa are under evaluation, representing the possible upcoming applications of these agents. Mechanisms of sensitization and resistance have been only partially elucidated. In our review, we summarize the current clinical evidence regarding PARPis in mPCa and the future directions of these targeted agents.
MeSH term(s)	Humans ; Antineoplastic Agents/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Precision Medicine ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology
Chemical Substances	Antineoplastic Agents ; Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2023-10-18
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2023.104157
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Article ; Online: SIUrO best practice recommendations to optimize BRCA 1/2 gene testing from DNA extracted from bone biopsy in mCRPC patients (BRCA Optimal Bone Biopsy Procedure: BOP).

Cimadamore, Alessia / Rescigno, Pasquale / Conteduca, Vincenza / Caliò, Anna / Allegritti, Massimiliano / Calò, Valentina / Montagnani, Ilaria / Lucianò, Roberta / Patruno, Margherita / Bracarda, Sergio

Virchows Archiv : an international journal of pathology

2023 Volume 483, Issue 5, Page(s) 579–589

Abstract: The main guidelines and recommendations for the implementation of the BRCA1/2 somatic test do not focus on the clinical application of predictive testing on bone metastases, a frequent condition in metastatic prostate cancer, by analyzing the critical ... ...

Abstract	The main guidelines and recommendations for the implementation of the BRCA1/2 somatic test do not focus on the clinical application of predictive testing on bone metastases, a frequent condition in metastatic prostate cancer, by analyzing the critical issues encountered by laboratory practice. Our goal is to produce a document (protocol) deriving from a multidisciplinary team approach to obtain high quality nucleic acids from biopsy of bone metastases. This document aims to compose an operational check-list of three phases: the pre-analytical phase concerns tumor cellularity, tissue processing, sample preservation (blood/FFPE), fixation and staining, but above all the decalcification process, the most critical phase because of its key role in allowing the extraction of somatic DNA with a good yield and high quality. The analytical phase involves the preparation of the libraries that can be analyzed in various NGS genetic sequencing platforms and with various bioinformatics software for the interpretation of sequence variants. Finally, the post-analytical phase that allows to report the variants of the BRCA1/2 genes in a clear and usable way to the clinician who will use these data to manage cancer therapy with PARP Inhibitors.
MeSH term(s)	Male ; Humans ; BRCA1 Protein/genetics ; Mutation ; BRCA2 Protein/genetics ; Prostatic Neoplasms, Castration-Resistant/diagnosis ; Prostatic Neoplasms, Castration-Resistant/genetics ; DNA ; Biopsy
Chemical Substances	BRCA1 protein, human ; BRCA1 Protein ; BRCA2 protein, human ; BRCA2 Protein ; DNA (9007-49-2)
Language	English
Publishing date	2023-10-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-023-03660-0
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Article ; Online: Biological Evolution of Castration-resistant Prostate Cancer.

Davies, Alastair / Conteduca, Vincenza / Zoubeidi, Amina / Beltran, Himisha

European urology focus

2019 Volume 5, Issue 2, Page(s) 147–154

Abstract: Context: Recent studies focused on the molecular characterization of metastatic prostate cancer have identified genomic subsets and emerging resistance patterns. Detection of these alterations in patients has potential implications for therapy selection ...

Abstract	Context: Recent studies focused on the molecular characterization of metastatic prostate cancer have identified genomic subsets and emerging resistance patterns. Detection of these alterations in patients has potential implications for therapy selection and prognostication. Objective: The primary objective is to review the current landscape of clinical and molecular biomarkers in advanced prostate cancer and understand how they may reflect underlying tumor biology. We also discuss how these features may potentially impact earlier stages of the disease. Evidence acquisition: A literature search was performed of recent clinical biomarker/genomic studies focused on advanced metastatic prostate cancer as well as relevant preclinical studies investigating how these alterations influence therapy response or resistance. Evidence synthesis: Metastatic castration-resistant prostate cancer is commonly driven by androgen receptor signaling even after progression on potent hormonal agents, but other alterations may also be present or emerge during therapy resistance such as DNA repair gene aberrations or combined loss of tumor suppressor genes. Biological implications of these changes are context dependent, which may affect their detection and interpretation. Conclusions: Molecular changes occur during prostate cancer progression and treatment resistance. Detection of genomic alterations has potential to influence therapy choice. Additional studies are warranted to elucidate the evolution of these changes and their impact in earlier stages of the disease. Patient summary: We review the biology of advanced prostate cancer, and highlight opportunities and challenges for using biological or molecular assays to help guide individualized treatment decisions for patients.
MeSH term(s)	Androgen Antagonists/therapeutic use ; Biomarkers/metabolism ; Disease Progression ; Genomics/methods ; Humans ; Male ; Molecular Biology/methods ; Neoplasm Metastasis/pathology ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/pathology ; Prostatic Neoplasms, Castration-Resistant/secondary ; Receptors, Androgen/drug effects ; Receptors, Androgen/genetics
Chemical Substances	Androgen Antagonists ; Biomarkers ; Receptors, Androgen
Language	English
Publishing date	2019-02-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	2405-4569
ISSN (online)	2405-4569
DOI	10.1016/j.euf.2019.01.016
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Article: Epigenetics in prostate cancer: clinical implications.

Conteduca, Vincenza / Hess, Judy / Yamada, Yasutaka / Ku, Sheng-Yu / Beltran, Himisha

Translational andrology and urology

2021 Volume 10, Issue 7, Page(s) 3104–3116

Abstract: Epigenetic alterations, including changes in DNA methylation, histone modifications and nucleosome remodeling, result in abnormal gene expression patterns that contribute to prostate tumor initiation and continue to evolve during the course of disease ... ...

Abstract	Epigenetic alterations, including changes in DNA methylation, histone modifications and nucleosome remodeling, result in abnormal gene expression patterns that contribute to prostate tumor initiation and continue to evolve during the course of disease progression. Epigenetic modifications are responsible for silencing tumor-suppressor genes, activating oncogenic drivers, and driving therapy resistance and thus have emerged as promising targets for antineoplastic therapy in prostate cancer. In this review, we discuss the role of epigenetics in prostate cancer with a particular emphasis on clinical implications. We review how epigenetic regulators crosstalk with critical biological pathways, including androgen receptor signaling, and how these interactions dynamically control prostate cancer transcriptional profiles. Because of their potentially reversible nature, restoration of a "normal" epigenome could provide a basis for innovative therapeutic strategies in prostate cancer. We highlight how particular epigenetic alterations are emerging as potential diagnostic and prognostic biomarkers and/or targets for the treatment of advanced prostate cancer.
Language	English
Publishing date	2021-08-25
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2851630-8
ISSN	2223-4691 ; 2223-4691 ; 2223-4683
ISSN (online)	2223-4691
ISSN	2223-4691 ; 2223-4683
DOI	10.21037/tau-20-1339
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