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自噬与化疗耐药:癌症治疗有前景的治疗靶点。

Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment.

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

出版信息

Cell Death Dis. 2013 Oct 10;4(10):e838. doi: 10.1038/cddis.2013.350.

Abstract

Induction of cell death and inhibition of cell survival are the main principles of cancer therapy. Resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anticancer drugs. A variety of factors contribute to drug resistance, including host factors, specific genetic or epigenetic alterations in the cancer cells and so on. Although various mechanisms by which cancer cells become resistant to anticancer drugs in the microenvironment have been well elucidated, how to circumvent this resistance to improve anticancer efficacy remains to be defined. Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles. Recently, several studies have shown that autophagy constitutes a potential target for cancer therapy and the induction of autophagy in response to therapeutics can be viewed as having a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance. Thus, understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.

摘要

诱导细胞死亡和抑制细胞存活是癌症治疗的主要原则。化疗耐药是肿瘤学中的一个主要问题,限制了抗癌药物的疗效。多种因素导致肿瘤细胞对化疗药物产生耐药性,包括宿主因素、癌细胞中特定的遗传或表观遗传改变等。尽管已经很好地阐明了癌细胞在微环境中对抗癌药物产生耐药性的各种机制,但如何克服这种耐药性以提高抗癌疗效仍有待确定。自噬是一种重要的细胞内稳态回收机制,现在作为应对代谢和治疗压力的关键参与者而出现,它试图通过过度或不必要的蛋白质和受损或衰老的细胞器的分解代谢来维持/恢复代谢平衡。最近,几项研究表明,自噬是癌症治疗的一个潜在靶点,并且对治疗的自噬诱导可以被视为具有促死亡或促存活作用,这有助于这些药物的抗癌疗效以及耐药性。因此,了解自噬的新功能可能使我们能够开发出有前途的治疗策略,以增强化疗效果并改善癌症患者的临床治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2110/3824660/c61926da0fef/cddis2013350f1.jpg

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