Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 12, Pages 4530-4535Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1401160111
Keywords
cancer stem cell; drug screening; Drosophila intestinal stem cell; whole-animal screening
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Funding
- Jane Coffin Childs Memorial Fund
- Charles King Trust
- Harvard University
- National Institutes of Health
- Howard Hughes Medical Institute (HHMI)
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Here we report the development of an in vivo system to study the interaction of stem cells with drugs using a tumor model in the adult Drosophila intestine. Strikingly, we find that some Food and Drug Administration-approved chemotherapeutics that can inhibit the growth of Drosophila tumor stem cells can paradoxically promote the hyperproliferation of their wild-type counterparts. These results reveal an unanticipated side effect on stem cells that may contribute to tumor recurrence. We propose that the same side effect may occur in humans based on our finding that it is driven in Drosophila by the evolutionarily conserved Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway. An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence.
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