Drosophila cancer models to identify inhibitors that block an optimized combination of kinase targets

2012 Science-Business eXchange  
Drosophila cancer models to identify inhibitors that block an optimized combination of kinase targets Screening in Drosophila cancer models could aid the identification of inhibitors against an optimized combination of kinase targets. In a Drosophila model of multiple endocrine neoplasia type 2 (MEN2), a disease caused by activating mutations in ret proto-oncogene (RET), screening a library of small molecules that inhibited RET and other kinases identified a lead molecule that caused some flies
more » ... to survive to adulthood. In the Drosophila model, the initial hit was optimized to block a combination of kinases to increase efficacy and decrease toxicity. In MEN2 mice, the lead molecule decreased tumor growth compared with Caprelsa vandetanib. Next steps include further optimizing the inhibitor and screening kinase inhibitor libraries in Drosophila models of additional cancers. Caprelsa, an inhibitor of RET and other kinases from AstraZeneca plc, is approved to treat advanced medullary thyroid cancer, a disease that can result from MEN2.
doi:10.1038/scibx.2012.711 fatcat:daacalgfyrchrdquijgr56m4tq