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Cancer Biol Ther. 2011 Jan 15;11(2):169-76. doi: 10.4161/cbt.11.2.14663.

Autophagy modulation for cancer therapy.

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1
Mayo Clinic and Mayo Cancer Center, 200 First Street SW, Rochester, MN 55905, USA.

Abstract

Autophagy is a homeostatic and catabolic process that enables the sequestration and lysosomal degradation of cytoplasmic organelles and proteins that is important for the maintenance of genomic stability and cell survival. Beclin 1 (+/- ) gene knockout mice are tumor prone, indicating a tumor suppressor role for autophagy. Autophagy is also mechanism of stress tolerance that maintains cell viability and can lead to tumor dormancy, progression, and therapeutic resistance. Many anticancer drugs induce cytotoxic stress that can activate pro-survival autophagy. In some contexts, excessive or prolonged autophagy can lead to tumor cell death. Inhibition of cytoprotective autophagy by genetic or pharmacological means has been shown to enhance anticancer drug-induced cell death, suggesting a novel therapeutic strategy. Studies are ongoing to define optimal strategies to modulate autophagy for cancer prevention and therapy, and to exploit it as a target for anticancer drug discovery.

PMID:
21263212
PMCID:
PMC3230308
DOI:
10.4161/cbt.11.2.14663
[Indexed for MEDLINE]
Free PMC Article
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