AR copy number and AR signaling-directed therapies in castration-resistant prostate cancer

Research output: Contribution to journalReview article

Abstract

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

Original languageEnglish
Pages (from-to)869-876
Number of pages8
JournalCurrent Cancer Drug Targets
Volume18
Issue number9
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Castration
Androgen Receptors
Prostatic Neoplasms
Therapeutics
Neoplasms
Patient Selection
Up-Regulation
Biomarkers
Clinical Trials
Hormones
Biopsy

Keywords

  • Androgen receptor
  • AR copy number
  • Biomarkers
  • CRPC
  • Outcome
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

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title = "AR copy number and AR signaling-directed therapies in castration-resistant prostate cancer",
abstract = "Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.",
keywords = "Androgen receptor, AR copy number, Biomarkers, CRPC, Outcome, Prostate cancer",
author = "Samanta Salvi and Vincenza Conteduca and Cristian Lolli and Sara Testoni and Valentina Casadio and Andrea Zaccheroni and Lorena Rossi and Burgio, {Salvatore Luca} and Cecilia Menna and Giuseppe Schepisi and {De Giorgi}, Ugo",
year = "2018",
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TY - JOUR

T1 - AR copy number and AR signaling-directed therapies in castration-resistant prostate cancer

AU - Salvi, Samanta

AU - Conteduca, Vincenza

AU - Lolli, Cristian

AU - Testoni, Sara

AU - Casadio, Valentina

AU - Zaccheroni, Andrea

AU - Rossi, Lorena

AU - Burgio, Salvatore Luca

AU - Menna, Cecilia

AU - Schepisi, Giuseppe

AU - De Giorgi, Ugo

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

AB - Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

KW - Androgen receptor

KW - AR copy number

KW - Biomarkers

KW - CRPC

KW - Outcome

KW - Prostate cancer

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