OCT 16, 2013 11:00 AM PDT

Embracing Complexity: Drosophila as a Tool to Develop Cancer Therapeutics

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  • Associate Dean of the Graduate School of Biological Sciences and Professor of Oncological Sciences, Icahn School of Medicine at Mount Sinai
      Dr. Cagan is a Professor in the Department of Developmental and Regenerative Biology and Associate Dean of the Graduate School of Biological Sciences of the Icahn School of Medicine at Mount Sinai. He is also Co-Founder of the biotechnology company Medros Inc. and Editor-in-Chief of Disease Models and Mechanisms. He is a world-renowned expert in the genetics of nervous system development and, more recently, Dr. Cagan has been a pioneer in using Drosophila for novel approaches to cancer and diabetes. Research in Dr. Cagans laboratory focuses on using the fruit fly Drosophila to develop complex models of diabetes and of breast, lung, colorectal, and thyroid cancers. Taking advantage of a century of powerful genetic tools, his laboratory has developed complex, multigenic disease models designed to model specific aspects of human disease. In addition to studying the mechanisms that direct cancer and diabetes, he has developed a novel robotics-based approach for screening whole animals for novel therapeutic drugs. This approach has helped identify the first chemotherapeutic for Medullary Thyroid Carcinoma, vandetanib. More recent work has used fly genetics to develop polypharmacological drugs and drug cocktails designed to address multiple pathways in a rational manner. His laboratory has also explored the links between diabetes and cancer, demonstrating how dietary sugar combines with specific oncogenes to render tumor insulin hypersensitive.


    Cancer and diabetes are complex diseases that have proven difficult to treat in the clinics. Until recently, most efforts have focused on hitting individual therapeutic targets cleanly. Unfortunately, success rates in clinical trials have been low: in the case of cancer, success rates for individual drugs have commonly been in single digits. This suggests that our models are poorly predictive of useful therapeutics. One issue is disease complexity. Another is the importance of modeling disease in the context of the whole animal. I will discuss our efforts using Drosophila to build complex cancer and diabetes models in the context of the whole animal. We utilize genomic sequencing data to create multi-hit fly models, either of disease populations or of individual patients. We then use automated systems to screen libraries for useful drugs. In addition, I will describe how we combine Drosophila genetics plus medicinal chemistry to create new generation candidate therapeutics.

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