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The autophagic paradox in cancer therapy

Oncogene volume 31, pages 939–953 (2012)Cite this article

Abstract

Autophagy, hallmarked by the formation of double-membrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a pro-survival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cell-fate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics.

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Acknowledgements

This work was supported by research grant from the CUHK Group Research Scheme (3110043) and CUHK Focused Investments Scheme-Scheme C.

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  1. LKS Institute of Health Sciences and Department of Medicine and Therapeutics, Institute of Digestive Diseases, The Chinese University of Hong Kong, Hong Kong, China

    W K K Wu, C H Cho, X J Wang, C W Lee, F K L Chan, J Yu & J J Y Sung

  2. Department of Infection & Immunity, Academic Unit of Inflammation & Tumour Targeting, University of Sheffield School of Medicine, Sheffield, UK

    S B Coffelt

  3. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    C H Cho

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Wu, W., Coffelt, S., Cho, C. et al. The autophagic paradox in cancer therapy. Oncogene 31, 939–953 (2012). https://doi.org/10.1038/onc.2011.295

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