Autophagy modulation for cancer therapy.
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.
Mayo Clinic and Mayo Cancer Center, 200 First Street SW, Rochester, MN 55905, USA.
Zhineng J
ZJ
Yang
Cheng E
CE
Chee
Shengbing
S
Huang
Frank
F
Sinicrope
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016923:Cell Death; D002470:Cell Survival; D002986:Clinical Trials as Topic; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy*
D016588:Anticarcinogenic Agents
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