Abstract 4206: Utilizing a Drosophila high throughput screening technology for cancer drug discovery

Abstract

Abstract MEDROS has developed unique high-throughput 96-well drug screening methods to model human diseases in the context of a whole organism, the fruit fly Drosophila melanogaster. Our approach is designed to address disease complexity and whole animal drug pharmacology, aspects poorly addressed by in vitro or cell screening methods. Here we focus on cancer, a complex disease that will benefit from the powerful tools available in Drosophila. We have designed a cancer fly model where the human oncogenes Ras and Src, centrally important in a variety of major human cancers, are targeted together to the retinal epithelium. We utilize inducible systems to calibrate their activation, generating reliably metastatic tumors that progress in a manner that is readily screened. In one iteration, these ‘tumors’ lead to organismal lethality that we have developed into a robust high-throughput screen. The kinase inhibitor Sorafenib rescued this phenotype, allowing flies to survive to adulthood and providing important validation of our screening platform. In a second iteration we permit Ras and Src to more mildly transform the eye epithelium to generate a ‘rough’ or ‘tumorous’ eye. We demonstrate that these phenotypes provide a second, more sensitive assay of Ras/Src oncogenic activity; again, Sorafenib rescued these cancer-like phenotypes. This work has important implications regarding novel drug screening methods for cancer and provides useful insights about the metastatic process. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4206.