Principles and current strategies for targeting autophagy for cancer treatment

Ravi K. Amaravadi, Jennifer Lippincott-Schwartz, Xiao-Ming Yin, William A. Weiss, Naoko Takebe, William Timmer, Robert S. DiPaola, Michael T. Lotze, Eileen White

Research output: Contribution to journalArticle

562 Citations (Scopus)

Abstract

Autophagy is an evolutionarily conserved, intracellular self-defense mechanism in which organelles and proteins are sequestered into autophagic vesicles that are subsequently degraded through fusion with lysosomes. Cells, thereby, prevent the toxic accumulation of damaged or unnecessary components, but also recycle these components to sustain metabolic homoeostasis. Heightened autophagy is a mechanism of resistance for cancer cells faced with metabolic and therapeutic stress, revealing opportunities for exploitation as a therapeutic target in cancer. We summarize recent developments in the field of autophagy and cancer and build upon the results presented at the Cancer Therapy Evaluation Program (CTEP) Early Drug Development meeting in March 2010. Herein, we describe our current understanding of the core components of the autophagy machinery and the functional relevance of autophagy within the tumor microenvironment, and we outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy, and immunotherapy. Finally, we describe ongoing clinical trials involving HCQ as a first generation autophagy inhibitor, as well as strategies for the development of novel, more potent, and specific inhibitors of autophagy.

Original languageEnglish
Pages (from-to)654-666
Number of pages13
JournalClinical Cancer Research
Volume17
Issue number4
DOIs
StatePublished - Feb 15 2011

Fingerprint

Autophagy
Neoplasms
Hydroxychloroquine
Therapeutics
Tumor Microenvironment
Poisons
Program Evaluation
Lysosomes
Organelles
Immunotherapy
Homeostasis
Clinical Trials
Drug Therapy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Amaravadi, R. K., Lippincott-Schwartz, J., Yin, X-M., Weiss, W. A., Takebe, N., Timmer, W., ... White, E. (2011). Principles and current strategies for targeting autophagy for cancer treatment. Clinical Cancer Research, 17(4), 654-666. https://doi.org/10.1158/1078-0432.CCR-10-2634

Principles and current strategies for targeting autophagy for cancer treatment. / Amaravadi, Ravi K.; Lippincott-Schwartz, Jennifer; Yin, Xiao-Ming; Weiss, William A.; Takebe, Naoko; Timmer, William; DiPaola, Robert S.; Lotze, Michael T.; White, Eileen.

In: Clinical Cancer Research, Vol. 17, No. 4, 15.02.2011, p. 654-666.

Research output: Contribution to journalArticle

Amaravadi, RK, Lippincott-Schwartz, J, Yin, X-M, Weiss, WA, Takebe, N, Timmer, W, DiPaola, RS, Lotze, MT & White, E 2011, 'Principles and current strategies for targeting autophagy for cancer treatment', Clinical Cancer Research, vol. 17, no. 4, pp. 654-666. https://doi.org/10.1158/1078-0432.CCR-10-2634
Amaravadi RK, Lippincott-Schwartz J, Yin X-M, Weiss WA, Takebe N, Timmer W et al. Principles and current strategies for targeting autophagy for cancer treatment. Clinical Cancer Research. 2011 Feb 15;17(4):654-666. https://doi.org/10.1158/1078-0432.CCR-10-2634
Amaravadi, Ravi K. ; Lippincott-Schwartz, Jennifer ; Yin, Xiao-Ming ; Weiss, William A. ; Takebe, Naoko ; Timmer, William ; DiPaola, Robert S. ; Lotze, Michael T. ; White, Eileen. / Principles and current strategies for targeting autophagy for cancer treatment. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 4. pp. 654-666.
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