Tumor cell autophagy as an adaptive response mediating resistance to treatments such as antiangiogenic therapy

Cancer Res. 2012 Sep 1;72(17):4294-9. doi: 10.1158/0008-5472.CAN-12-1076. Epub 2012 Aug 22.

Abstract

Autophagy is a lysosomal degradation pathway that can sequester cytosolic material, including organelles, nonspecifically in a process called nonselective macroautophagy, or target specific protein aggregates designated for destruction in a process called selective autophagy. Autophagy is one mechanism that enables tumor cells to survive stressors in the tumor microenvironment, as well as injuries caused by treatments such as chemotherapy and radiation therapy. The complexity of the role of autophagy in cancer is underscored by evidence that autophagy can allow premalignant cells to escape the genotoxic stress and inflammation that promote tumorigenesis, and that some tumor cells exhibit loss of autophagy capacity altogether through molecular mechanisms that have not yet been defined. Efforts to understand and modulate the autophagy pathway will be crucial to maximize the full therapeutic potential of cancer therapies that are currently hindered by tumor cell autophagy as a resistance mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Biological*
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Autophagy* / drug effects
  • Chloroquine / pharmacology
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Tumor Microenvironment

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Chloroquine