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Drug screening in Drosophila; why, when, and when not?

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Abstract The best global seller among oncology drugs in 2018 is lenalidomide, an analog of thalidomide. It took 53 years and a circuitous route from the discovery of thalidomide to approval of an analog for use in treatment of cancer. We understand now a lot more about the genetic and molecular basis of diseases than we did in 1953 when thalidomide was discovered. We have also no shortage of chemical libraries with hundreds of thousands of compounds, both synthetic and natural. What we need are better ways to search among these rich resources for compounds with the potential to do what we want them to do. This review summarizes examples from the literature that make Drosophila melanogaster a good model to screen for drugs, and discusses knowledge gaps and technical challenges that make Drosophila models not as widely used as they could or should be. This article is categorized under: Technologies > Analysis of Cell, Tissue, and Animal Phenotypes
The canonical Wnt pathway, without (a) and with (b) ligand [after (Clevers, )]. Only the components discussed in this review are shown
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The traumatic brain injury machine (Katzenberger et al., ), before (a) and after (b) the strike. (c,d) show flies at the corresponding states
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Screen for modulators of radiation (Gladstone & Su, ). Third instar larvae were “sized” by passing through sieves and irradiated en mass. Irradiated larvae were aliquoted into culture vials that contained one drug per vial mixed with the food. Survival to adulthood (“eclosion”) was quantified 10 days later by counting empty (live) and full (dead) pupa cases
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A screen for drugs that inhibit the growth of intestinal stem cell‐derived tumors (Markstein et al., ). (a) Flies harboring luciferase‐expressing tumors were treated with drugs in 96‐well plates. Flies were homogenized and luciferase activity measured to quantify drug effect. (b) A sample dataset with 15 compounds
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