Targeting endothelin-1 receptor/β-arrestin1 network for the treatment of ovarian cancer
Targeting endothelin-1 receptor/β-arrestin1 network for the treatment of ovarian cancer
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靶向内皮素-1受体/β-arrestin1网络治疗卵巢癌
DOI：
10.1080/14728222.2017.1361930
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发表时间：
2017
影响因子：
5.8
通讯作者：
A. Bagnato
中科院分区：
文献类型：
--
作者：
L. Rosanò;Roberta Cianfrocca;Rosanna Sestito;Piera Tocci;V. Di Castro;A. Bagnato
摘要：简介：内皮素 1 受体 (ET-1R)/β-arrestin1 (β-arr1) 信号在卵巢癌中失调。这种信号传导回路使癌细胞能够参与多个普遍交织在一起的信号传导和转录网络，并代表了开发卵巢癌治疗新药物的潜在治疗靶点。涵盖领域：在本文中，我们讨论了 ET-1R 与支架蛋白 β-arr1 介导的关键通路之间的信号网络的作用，作为信号复合物的一部分，或作为转录共激活剂，促进对包括 ET-1 在内的不同基因的转录的精确控制。因此，ET-1R/β-arr1 是一个可操作的节点，参与激活有助于旁路信令的持续反馈环路。以 ET-1R 为靶点，增强该回路的能力是达到临床疗效的必要措施。临床前研究表明，FDA 批准的双重 ETAR/ETBR 拮抗剂阻断 ET-1R 可阻止 β-arr1 网络形成，为卵巢癌患者提供一种新颖的治疗策略。专家意见：本次综述中提供的有关 ET-1R/β-arr1 中心的信息是一个宝贵的工具，可用于识别与卵巢癌相关的相互关联的通路并更有效地靶向它们。 ET-1R 疗法产生的新观点可能会为设计新的有前途的组合疗法（阻断补偿网络）提供一个有价值的框架。
ABSTRACT Introduction: Endothelin-1 receptor (ET-1R)/β-arrestin1 (β-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 β-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/β-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 β-arr1 network formation, offering a novel therapeutic strategy in ovarian cancer patients. Expert opinion: The information provided in this review about the ET-1R/β-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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