Significance In this article we report a large-scale chemical screen in adult Drosophila to find inhibitors of stem-cell–derived tumors. To our surprise, we found that some Food and Drug Administration-approved chemotherapy drugs have the dual property of reducing growth of stem-cell–derived tumors while also stimulating hyperproliferation of their wild-type counterparts. Since hyperproliferation is one of the hallmarks of cancer cells, this side effect could contribute to refueling the growth of the very tumors that these chemotherapeutics are intended to inhibit. We show that this side effect is driven by the evolutionarily conserved Janus kinase-signal transducers and activators of transcription (JAK-STAT) inflammatory pathway, raising the possibility that the JAK-STAT pathway may also be activated in humans who are treated with some chemotherapeutics.

One of the most dramatic examples of programmed cell death occurs during Drosophila metamorphosis, when most of the larval tissues are destroyed in a process termed histolysis. Much of our understanding of this process comes from analyses of salivary gland and midgut cell death. In contrast, relatively little is known about the degradation of the larval musculature. Here, we analyze the programmed destruction of the abdominal dorsal exterior oblique muscle (DEOM) which occurs during the first 24 hrs of metamorphosis. We find that ecdysone signaling through Ecdysone receptor isoform B1 is required cell autonomously for the muscle death. Furthermore, we show that the orphan nuclear receptor FTZ-F1, opposed by another nuclear receptor, HR39, plays a critical role in the timing of DEOM histolysis. Finally, we show that unlike the histolysis of salivary gland and midgut, abdominal muscle death occurs by apoptosis, and does not require autophagy. Thus, there is no set rule as to the role of autophagy and apoptosis during Drosophila histolysis.