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

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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

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