The autophagic paradox in cancer therapy

Wu, W.K.K., Coffelt, S.B. , Cho, C.H., Wang, X.J., Lee, C.W., Chan, F.K.L., Yu, J. and Sung, J.J.Y. (2012) The autophagic paradox in cancer therapy. Oncogene, 31(8), pp. 939-953. (doi:10.1038/onc.2011.295) (PMID:21765470)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coffelt, Dr Seth
Authors: Wu, W.K.K., Coffelt, S.B., Cho, C.H., Wang, X.J., Lee, C.W., Chan, F.K.L., Yu, J., and Sung, J.J.Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:18 July 2011

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