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靶向自噬增强溶瘤病毒的癌症治疗。

Targeting autophagy to enhance oncolytic virus-based cancer therapy.

机构信息

Dalian Medical University Cancer Center, Institute of Cancer Stem Cell, 9 Lvshun Road South, Dalian 116044, Chin.

出版信息

Expert Opin Biol Ther. 2013 Jun;13(6):863-73. doi: 10.1517/14712598.2013.774365. Epub 2013 Mar 14.

Abstract

INTRODUCTION

Autophagy is a conserved catabolic process crucial in maintaining cellular homeostasis. On infection, oncolytic viruses (OVs) perturb the cellular autophagy machinery in infected tumor cells both in vitro and in vivo. Currently, pharmacological modulation of autophagy in OV-infected tumor cells has been shown to augment OV-mediated antitumor effects in preclinical studies. Combination of OVs with autophagy modulators can, therefore, have many potential applications in the future research on targeting autophagy and novel anticancer therapies.

AREAS COVERED

This review provides a detailed description of known interactions between OVs and autophagy and summarizes the roles of autophagy in OV replication and cell lysis. The recent literature on targeting autophagy with either the autophagy inducers, such as rapamycin, or autophagy inhibitors, such as chloroquine, to increase OV-induced cytotoxicity is reviewed to help researchers in further investigations. The major challenge for investigators is to understand the molecular mechanism underlying the interplay between OV and the autophagy machinery and its effect on oncolysis.

EXPERT OPINION

Targeting the cellular autophagy machinery could be explored as a new therapeutic strategy to enhance OV-mediated antitumor effects in the future.

摘要

简介

自噬是一种保守的分解代谢过程,对维持细胞内稳态至关重要。在体外和体内感染时,溶瘤病毒(OVs)都会扰乱受感染肿瘤细胞中的细胞自噬机制。目前,在临床前研究中已经表明,在 OV 感染的肿瘤细胞中,通过药理学方法调节自噬可以增强 OV 介导的抗肿瘤作用。因此,OV 与自噬调节剂的联合应用在未来针对自噬的靶向研究和新型抗癌疗法中有很大的应用潜力。

涵盖领域

本综述详细描述了 OVs 与自噬之间已知的相互作用,并总结了自噬在 OV 复制和细胞裂解中的作用。综述了近期关于使用自噬诱导剂(如雷帕霉素)或自噬抑制剂(如氯喹)靶向自噬以增加 OV 诱导的细胞毒性的文献,以帮助研究人员进一步研究。研究人员的主要挑战是了解 OV 与自噬机制之间相互作用的分子机制及其对溶瘤作用的影响。

专家意见

未来,靶向细胞自噬机制可能被探索作为一种增强 OV 介导的抗肿瘤作用的新治疗策略。

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