title: The autophagic paradox in cancer therapy.
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.
authors.affiliation: Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. wukakei@cuhk.edu.hk
authors.forename: W K K
authors.initials: WK
authors.lastname: Wu
authors.forename: S B
authors.initials: SB
authors.lastname: Coffelt
authors.forename: C H
authors.initials: CH
authors.lastname: Cho
authors.forename: X J
authors.initials: XJ
authors.lastname: Wang
authors.forename: C W
authors.initials: CW
authors.lastname: Lee
authors.forename: F K L
authors.initials: FK
authors.lastname: Chan
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: J J Y
authors.initials: JJ
authors.lastname: Sung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins