Transgenic Drosophila As A Drugscreening Tool In Multiple Cancers

Introduction: The selection of appropriate anticancer drugs in patients is a great challenge in cancer treatment. As medicine seeks to understand the difference between the “average” tumor and a tumor in an individual patient, there is great uncertainty regarding the effect of particular genes and drugs that target them. Transgenic Drosophila melanogaster has been proposed as a rapid and efficient system in which to generate a reliable model of an individual tumor and phenotypic screen for effective drugs. Such screens can potentially lead to the identification of a molecule that modifies a cancer phenotype by acting on a previously undescribed target or by acting simultaneously on more than one target.Methods: 97 Patients were assessed for genomic and clinical data. 12 patients had tumor genetics analyzed and models created that comprised driver mutations. 3 models were attempted in Drosophila and tested against 19 anticancer drugs.Results: 1 of 3 models was technically successful and advanced to drug screening. 5 drugs (gemcitabine, trametinib, crizotinib, doxorubicin, docetaxel) were predicted by the model to be effective against that particular cancer. However, neither of the two drugs used in the corresponding patient were predicted to be successful.Conclusions: While this project was unable to concretely validate the Drosophila modeling approach by accurately predicting treatment outcomes. I was able to develop and advance methods to predict the effects of a gene within a tumor and to develop one complete Drosophila model that responded to anticancer drugs in a dose-dependent manner. Further research is needed to assess the predictive value of these models.