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Title: Autophagy inhibition and antimalarials promote cell death in gastrointestinal stromal tumor (GIST)
Authors: Gupta, Anu ×
Roy, Srirupa
Lazar, Alexander J F
Wang, Wei-Lien
McAuliffe, John C
Reynoso, David
McMahon, James
Taguchi, Takahiro
Floris, Guiseppe
Debiec-Rychter, Maria
Schöffski, Patrick
Trent, Jonathan A
Debnath, Jayanta
Rubin, Brian P #
Issue Date: 2010
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:107 issue:32 pages:14333-14338
Abstract: Although gastrointestinal stromal tumors (GISTs) harboring activating KIT or platelet-derived growth factor receptor A (PDGFRA) mutations respond to treatment with targeted KIT/PDGFRA inhibitors such as imatinib mesylate, these treatments are rarely curative. Most often, a sizeable tumor cell subpopulation survives and remains quiescent for years, eventually resulting in acquired resistance and treatment failure. Here, we report that imatinib induces autophagy as a survival pathway in quiescent GIST cells. Inhibiting autophagy, using RNAi-mediated silencing of autophagy regulators (ATGs) or antimalarial lysosomotrophic agents, promotes the death of GIST cells both in vitro and in vivo. Thus, combining imatinib with autophagy inhibition represents a potentially valuable strategy to promote GIST cytotoxicity and to diminish both cellular quiescence and acquired resistance in GIST patients.
URI: 
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Experimental Oncology
Laboratory for Genetics of Malignant Disorders
Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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