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Nat Rev Drug Discov. 2017 Jul;16(7):487-511. doi: 10.1038/nrd.2017.22. Epub 2017 May 19.

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles.

Galluzzi L1,2, Bravo-San Pedro JM2,3,4,5,6, Levine B7,8, Green DR9, Kroemer G2,3,4,5,6,10,11.

Author information

1
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York 10065, USA.
2
Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris 75006, France.
3
Université Pierre et Marie Curie/Paris VI, Paris 75006, France.
4
Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris 75006, France.
5
INSERM, U1138, Paris 75006, France.
6
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif 94805, France.
7
Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
8
Howard Hughes Medical Institute, Dallas, Texas 75390, USA.
9
St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
10
Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm 17176, Sweden.
11
Pôle de Biologie, Hopitâl Européen George Pompidou (AP-HP), Paris 75015, France.

Abstract

Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic.

PMID:
28529316
PMCID:
PMC5713640
DOI:
10.1038/nrd.2017.22
[Indexed for MEDLINE]
Free PMC Article

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