Screening for Anti‐cancer Drugs in Drosophila


The vinegar fly, Drosophila melanogaster, has been a cornerstone of genetic analysis and cell and developmental biology research for over 100 years. Within the last decade, Drosophila is making its mark in translational research in its utilisation in modelling human diseases and in screens for small molecule inhibitors. In particular, its use in modelling cancer development and in identifying anti‐cancer therapeutics is beginning to make an important contribution to the current drug discovery pipeline, which to date has been only poorly successful in delivering drugs, identified in vitro, into the clinic for anti‐cancer therapy. The primary advantages of the Drosophila system for use in anti‐cancer drug screening are the conservation of cancer genes/pathways between flies and mammals, its suitability for rapid phenotypic screening of chemicals for anti‐cancer effects in vivo in a high‐throughput and cost‐effective manner and its use in identifying drugs that can specifically target tumours in vivo.

Key Concepts

  • The current drug screening pipeline has been only poorly efficient in progressing anti‐cancer drugs to the clinic because of differences between in vitro and in vivo systems
  • Drosophila melanogaster is an excellent model organism for cost‐effective high‐throughput in vivo screening for anti‐cancer compounds relevant to human cancer
  • Drosophila larvae or adults can be readily screened in a high‐throughput manner for the effect of orally administered compounds on a particular phenotype using phenotypic or fluorescent read‐outs
  • Drosophila models of cancer used for chemical screens include those generated by expression of cancer‐causing genes, whole animal synthetic lethality with radiation and specific cancer phenotypes
  • Biological and technical limitations of Drosophila might restrict the discovery of compounds and their translation into the clinic
  • Screening of orally administered drugs in flies has already proven to be successful in identifying new compounds or FDA‐approved compounds for use in cancer therapy

Keywords: Drosophila; chemical screening; anti‐cancer drugs; cancer; signalling pathways; multiple endocrine neoplasia type 2; polypharmachological compounds; glutamate utilisation inhibitors; translational inhibitors; combination therapy

Figure 1. Chemical screening in Drosophila models of cancer.
Figure 2. Post screen – mechanism, drug refinement and translation to the clinic.


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Further Reading

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Richardson, Helena E, Willoughby, Lee, and Humbert, Patrick O(Mar 2015) Screening for Anti‐cancer Drugs in Drosophila. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022535]