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羟氯喹啉与自噬抑制剂在癌症方面的研究进展

Research progress of hydroxychloroquine and autophagy inhibitors on cancer.

作者信息

Shi Ting-Ting, Yu Xiao-Xu, Yan Li-Jun, Xiao Hong-Tao

机构信息

School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Department of Otolaryngology, Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital, Chengdu, China.

出版信息

Cancer Chemother Pharmacol. 2017 Feb;79(2):287-294. doi: 10.1007/s00280-016-3197-1. Epub 2016 Nov 26.

Abstract

PURPOSE

Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed.

METHODS

A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study.

RESULTS

Many preclinical studies indicate that the combination of HCQ with chemotherapies or radiotherapies may enhance the effect of anticancer, providing base for launching cancer clinical trials involving HCQ. The new and more sensitive diagnostic techniques report a prevalence of HCQ retinopathy up to 7.5%. Lys05, SAR405, verteporfin, VATG-027, mefloquine and spautin-1 may be potent autophagy inhibitors.

CONCLUSION

Additional mechanistic studies of HCQ in preclinical models are still required in order to answer these questions whether HCQ actually inhibits autophagy in non-selective tumors and whether the extent of inhibition would be sufficient to alter chemotherapy or radiotherapy sensitivity.

摘要

目的

羟氯喹(HCQ)是氯喹的类似物,在当前临床试验中可增强化疗和放疗对多种肿瘤的疗效。同时,HCQ视网膜病变的毒性引起了全球关注。因此,迫切需要有效的自噬抑制剂。

方法

对“羟氯喹”或“氯喹”与“临床试验”、“视网膜病变”和“新型自噬抑制剂”进行系统综述。这导致了许多涉及HCQ的交叉参考文献,这些数据已纳入以下研究。

结果

许多临床前研究表明,HCQ与化疗或放疗联合使用可能增强抗癌效果,为开展涉及HCQ的癌症临床试验提供了依据。新的、更敏感的诊断技术报告HCQ视网膜病变的患病率高达7.5%。Lys05、SAR405、维替泊芬、VATG-027、甲氟喹和spautin-1可能是有效的自噬抑制剂。

结论

仍需要在临床前模型中对HCQ进行更多的机制研究,以回答这些问题,即HCQ是否真的在非选择性肿瘤中抑制自噬,以及抑制程度是否足以改变化疗或放疗敏感性。

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