Small Molecule Inhibitors of Twist1 Function to Inhibit Tumor Progression
The Twist1 gene is highly expressed in many different tumor types and regulates several different stages of tumor development, from initiation through metastasis. Loss of Twist1 can prevent tumor progression, and therefore Twist1 represents a promising target for the development of anti-cancer drugs. Dr. Spicer and his team have identified specific protein interactions that are required for Twist1 function. Consequently this project aims to develop primary and secondary assays for high throughput screening to identify small molecule inhibitors of these interactions and to validate these assays with a small-scale screen of 2,000 compounds. The long-range goal is to extend this initial study to a large-scale screen of more than 500,000 compounds in collaboration with the Broad Institute in Boston. There is now a growing literature on the importance of Twist1 in promoting tumor progression in many different tumor types, and therefore an agent targeting Twist1 function would have broad therapeutic value.