In a newly published article, the researchers reported a large-scale chemical screen in adult Drosophila to find inhibitors of stem-cell–derived tumors. They 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. It shows 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. An immediate implication of these findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence.
These results in the fly may seem surprising. But recent work by others reported a similar effect in the drug doxorubicin in mice: doxorubicin induced cells to overgrow by triggering the TNF-alpha pathway while in flies several chemotherapy drugs, including doxorubicin, triggered JAK-STAT pathway which has been conserved through evolution in both flies and humans. Both pathways trigger the inflammatory response, which is generally associated with cancer.