The role of autophagy in anticancer therapy: promises and uncertainties

. Tschan MP, Simon H‐U. (Department of Medical Oncology, Inselspital, Bern University Hospital; and Institute of Pharmacology, University of Bern; Bern, Switzerland) The role of autophagy in anticancer therapy: promises and uncertainties (Symposium). J Intern Med 2010; 268: 410–418. Autophagy (literally self‐eating) is a catabolic mechanism involved in the recycling and turnover of cytoplasmic constituents. Although often referred to as type II programmed cell death, autophagy is primarily a survival rather than a cell death mechanism in response to different stress stimuli. Autophagy is a process in which part of the cytoplasm or entire organelles are sequestered into double‐membrane vesicles, called autophagosomes, which ultimately fuse with lysosomes to degrade their contents. Studies show that autophagy is associated with a number of pathological conditions, including cancer, infectious diseases, myopathies and neurodegenerative disorders. With respect to cancer, it has been suggested that the early stages of tumourigenesis are associated with downregulation of autophagy‐related (ATG) genes. Indeed, several ATG genes display tumour suppressor function, including Beclin1, which is frequently hemizygously deleted in breast cancer cells. Conversely, in advanced stages of tumourigenesis or during anticancer therapy, autophagy may promote survival of tumour cells in adverse environmental conditions. Therefore, a thorough understanding of autophagy in different cancer types and stages is a prerequisite to determine an autophagy‐activating or autophagy‐inhibiting treatment strategy.