*Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow G12 0ZD, U.K.
Essays Biochem. 2013;55:133-51. doi: 10.1042/bse0550133.
Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.
自噬是一种发生在所有哺乳动物细胞中的过程,可确保细胞内的稳态和质量控制。自噬(自噬[自体]-吞噬(phagy))一词于 1963 年由 Christian de Duve 首次提出,他发现溶酶体参与自噬过程。此后,人们在理解自噬的分子机制和信号调控方面取得了重大进展,并且发表了几篇综述,全面总结了这些发现。自噬在癌症中的作用在过去几年中受到了广泛关注,目前正在进行几项临床试验来测试自噬调节剂。在本章中,我们旨在简要概述自噬的机制和关键调控因子的最新发现,并讨论哺乳动物自噬在健康和疾病中的重要生理作用。特别关注自噬在癌症预防、发展以及对癌症治疗的反应中的作用。在这方面,我们还提供了一份最新的列表,并讨论了目前旨在单独或联合放射、化学或靶向治疗来调节自噬以增强抗癌干预的临床试验。