Targeting endothelin-1 receptor/beta-arrestin1 network for the treatment of ovarian cancer

L. Rosano, R. Cianfrocca, R. Sestito, P. Tocci, V. Di Castro, A. Bagnato

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Endothelin-1 receptor (ET-1R)/beta-arrestin1 (beta-arr1) signaling is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to engage several signaling and transcriptional networks that are pervasively intertwined, and represent a potential therapeutic target for developing novel agents for ovarian cancer treatment. Areas covered: In this article, we discuss the role of the signaling network between ET-1R and key pathways mediated by the scaffold protein beta-arr1, as part of signaling complex, or as a transcription co-activator, promoting precise control of transcription of different genes, including ET-1. Therefore ET-1R/beta-arr1 is an actionable node involved in the activation of a persistent feedback loop that contributes to bypass signaling. Targeting ET-1R empowering this circuit can represent a necessary measure to reach clinical efficacy. Preclinical studies demonstrate that blocking ET-1R by FDA approved dual ETAR/ETBR antagonist prevents beta-arr1 network formation, offering a novel therapeutic strategy in ovarian cancer patients. Expert opinion: The information provided in this review about the ET-1R/beta-arr1 hub represents an invaluable tool for both identifying the interconnected pathways involved in ovarian cancer and targeting them more effectively. The new perspective arising from ET-1R therapeutics will likely prompt a valuable frame for the design of new promising combinatorial therapy, blocking compensatory networks.
Original languageEnglish
Pages (from-to)925-932
Number of pages8
JournalExpert Opinion on Therapeutic Targets
Volume21
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

Endothelin A Receptors
Ovarian Neoplasms
Transcription
Therapeutics
Oncology
Networks (circuits)
Gene Regulatory Networks
Expert Testimony
Scaffolds
Genes
Chemical activation
Cells
Feedback

Keywords

  • Antineoplastic Agents/pharmacology
  • Drug Design
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Ovarian Neoplasms/drug therapy/pathology
  • Receptor, Endothelin A/drug effects/metabolism
  • Receptor, Endothelin B/drug effects/metabolism
  • Signal Transduction
  • beta-Arrestin 1/metabolism
  • ET-1 receptor antagonist
  • ET-1 receptors
  • Endothelin-1
  • ovarian cancer
  • therapeutic target
  • beta-arrestin-1

Cite this

Targeting endothelin-1 receptor/beta-arrestin1 network for the treatment of ovarian cancer. / Rosano, L.; Cianfrocca, R.; Sestito, R.; Tocci, P.; Castro, V. Di; Bagnato, A.

In: Expert Opinion on Therapeutic Targets, Vol. 21, No. 10, 01.10.2017, p. 925-932.

Research output: Contribution to journalArticle

Rosano, L. ; Cianfrocca, R. ; Sestito, R. ; Tocci, P. ; Castro, V. Di ; Bagnato, A. / Targeting endothelin-1 receptor/beta-arrestin1 network for the treatment of ovarian cancer. In: Expert Opinion on Therapeutic Targets. 2017 ; Vol. 21, No. 10. pp. 925-932.
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AU - Tocci, P.

AU - Castro, V. Di

AU - Bagnato, A.

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N2 - INTRODUCTION: Endothelin-1 receptor (ET-1R)/beta-arrestin1 (beta-arr1) signaling is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to engage several signaling and transcriptional networks that are pervasively intertwined, and represent a potential therapeutic target for developing novel agents for ovarian cancer treatment. Areas covered: In this article, we discuss the role of the signaling network between ET-1R and key pathways mediated by the scaffold protein beta-arr1, as part of signaling complex, or as a transcription co-activator, promoting precise control of transcription of different genes, including ET-1. Therefore ET-1R/beta-arr1 is an actionable node involved in the activation of a persistent feedback loop that contributes to bypass signaling. Targeting ET-1R empowering this circuit can represent a necessary measure to reach clinical efficacy. Preclinical studies demonstrate that blocking ET-1R by FDA approved dual ETAR/ETBR antagonist prevents beta-arr1 network formation, offering a novel therapeutic strategy in ovarian cancer patients. Expert opinion: The information provided in this review about the ET-1R/beta-arr1 hub represents an invaluable tool for both identifying the interconnected pathways involved in ovarian cancer and targeting them more effectively. The new perspective arising from ET-1R therapeutics will likely prompt a valuable frame for the design of new promising combinatorial therapy, blocking compensatory networks.

AB - INTRODUCTION: Endothelin-1 receptor (ET-1R)/beta-arrestin1 (beta-arr1) signaling is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to engage several signaling and transcriptional networks that are pervasively intertwined, and represent a potential therapeutic target for developing novel agents for ovarian cancer treatment. Areas covered: In this article, we discuss the role of the signaling network between ET-1R and key pathways mediated by the scaffold protein beta-arr1, as part of signaling complex, or as a transcription co-activator, promoting precise control of transcription of different genes, including ET-1. Therefore ET-1R/beta-arr1 is an actionable node involved in the activation of a persistent feedback loop that contributes to bypass signaling. Targeting ET-1R empowering this circuit can represent a necessary measure to reach clinical efficacy. Preclinical studies demonstrate that blocking ET-1R by FDA approved dual ETAR/ETBR antagonist prevents beta-arr1 network formation, offering a novel therapeutic strategy in ovarian cancer patients. Expert opinion: The information provided in this review about the ET-1R/beta-arr1 hub represents an invaluable tool for both identifying the interconnected pathways involved in ovarian cancer and targeting them more effectively. The new perspective arising from ET-1R therapeutics will likely prompt a valuable frame for the design of new promising combinatorial therapy, blocking compensatory networks.

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KW - ET-1 receptors

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JF - Expert Opinion on Therapeutic Targets

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