Abstract

My laboratory uses Drosophila to explore issues of cancer and diabetes. In this lecture I will focus on two aspects of cancer: multigenic model systems and drug discovery. We have constructed multigenic cancer models that reflect the complexity observed in individual human tumors including thyroid, breast, lung, and colorectal tumors. Combining oncogenes and tumor suppressors lead to emergent phenotypic complexity and differential sensitivity to patient-relevant drugs.

Using robotics-based whole animal drug approaches, we combined fly genetics and medicinal chemistry modeling to develop multi-targeting ‘polypharmacology’-based lead compounds. These compounds hold the promise of addressing tumor complexity while rationally avoiding 'anti-targets' that promote whole animal toxicity. I will also discuss related efforts linking metabolic disease with tumor progression, and how mechanism-based studies suggest specific drug cocktails.Finally, I will discuss our efforts to bring these approaches to individual patients in a 'bottom-up' screen for broadly useful therapeutics.