You eat what you are: Autophagy inhibition as a therapeutic strategy in leukemia

A. R. Sehgal, H. Konig, D. E. Johnson, D. Tang, R. K. Amaravadi, M. Boyiadzis, M. T. Lotze

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

A deeper understanding of the role of autophagy, literally 'self-eating', in normal and cancer cell biology has emerged over the last few years. Autophagy serves as a vehicle for cells to respond to various stressors including genomic, hypoxic and nutrient stress, and to oppose mechanisms of 'programmed' cell death. Here, we review not only mechanisms of cell death and cell survival but also the early successes in applying autophagy inhibition strategies in solid tumors using the only currently available clinical inhibitor, oral hydroxychloroquine. In acute leukemia, currently available chemotherapy drugs promote cell death and demonstrate clinical benefit, but relapse and subsequent chemotherapy resistance is common. Increasing preclinical data suggest that autophagy is active in leukemia as a means of promoting cell survival in response to chemotherapy. We propose coupling autophagy inhibition strategies with current cytotoxic chemotherapy and discuss synergistic combinations of available anti-leukemic therapies with autophagy inhibition. Furthermore, novel autophagy inhibitors are in development and promise to provide new therapeutic opportunities for patients with leukemia.

Original languageEnglish (US)
Pages (from-to)517-525
Number of pages9
JournalLeukemia
Volume29
Issue number3
DOIs
StatePublished - Mar 9 2015

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Sehgal, A. R., Konig, H., Johnson, D. E., Tang, D., Amaravadi, R. K., Boyiadzis, M., & Lotze, M. T. (2015). You eat what you are: Autophagy inhibition as a therapeutic strategy in leukemia. Leukemia, 29(3), 517-525. https://doi.org/10.1038/leu.2014.349