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Critical Reviews™ in Eukaryotic Gene Expression
IF: 1.841 5-Year IF: 1.927 SJR: 0.627 SNIP: 0.516 CiteScore™: 1.96

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v21.i1.50
pages 71-100

Autophagy in tumor suppression and cancer therapy

Che-Pei Kung
Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
Anna Budina
Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Gregor Balaburski
Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Marika K. Bergenstock
3D Biotek LLC, North Brunswick, New Jersey, USA
Maureen Murphy
Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

ABSTRACT

Autophagy is a stress-induced cell survival program whereby cells under metabolic, proteotoxic, or other stress remove dysfunctional organelles and/or misfolded/polyubiquitylated proteins by shuttling them via specialized structures called autophagosomes to the lysosome for degradation. The end result is the release of free amino acids and metabolites for use in cell survival. For tumor cells, autophagy is a double-edged sword: autophagy genes are frequently mono-allelically deleted, silenced, or mutated in human tumors, resulting in an environment of increased oxidative stress that is conducive to DNA damage, genomic instability, and tumor progression. As such, autophagy is tumor suppressive. In contrast, it is important to note that although tumor cells have reduced levels of autophagy, they do not eliminate this pathway completely. Furthermore, the exposure of tumor cells to an environment of increased metabolic and other stresses renders them reliant on basal autophagy for survival. Therefore, autophagy inhibition is an active avenue for the identification of novel anti-cancer therapies. Not surprisingly, the field of autophagy and cancer has experienced an explosion of research in the past 10 years. This review covers the basic mechanisms of autophagy, discusses its role in tumor suppression and cancer therapy, and posits emerging questions for the future.


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