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Research progress of hydroxychloroquine and autophagy inhibitors on cancer

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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.

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Acknowledgements

This work was funded by the Science and Technology Program of Sichuan Province (Grant Nos: 2009SZ0226, 2014FZ0103, 2015JQO027, 2015ZR0160) and the health department of Sichuan Province (Grant Nos: 100491, 120111) and Chengdu City Science and technology project (Grant No: 11PPYB010SF-289) and Young Scholars foundation of Sichuan Provincial People’s Hospital (Grant Nos: 30305030606, 303050308590).

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    Authors and Affiliations

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

      Ting-Ting Shi & Hong-Tao Xiao

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

      Xiao-Xu Yu

    3. Department of Pharmacy, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Chengdu, China

      Hong-Tao Xiao

    4. Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China

      Hong-Tao Xiao

    5. Department of Orthopedics, Xiangyang Central Hospital, Xiangyang, China

      Li-Jun Yan

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    Ting-Ting Shi and Xiao-Xu Yu have contributed equally to this work and should be considered co-first authors.

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    Shi, TT., Yu, XX., Yan, LJ. et al. Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother Pharmacol 79, 287–294 (2017). https://doi.org/10.1007/s00280-016-3197-1

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