Funded by the Constellation Gold Network Distributors
Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Many NSCLCs are caused by exposure to carcinogens, such as cigarette smoke, which cause changes to a cell’s DNA. These genetic changes can be detected by DNA sequencing methods. Next generation sequencing of tumors can provide clinicians, patients, and researchers with essential knowledge about the genes and proteins that cause and contribute to disease. Unfortunately, most human proteins (>95%) remain undrugged or inaccessible to labeling by FDA approved small molecules. Consequently, most cancer-associated proteins identified by DNA sequencing cannot be drugged. Therefore, we need new methods to identify druggable pockets in cancer-causing proteins. Our research develops such technology. In this study, we will develop a new approach to translate genetic changes into therapies. Our first step is to identify drug vulnerabilities that are specific to tumors. We will achieve this goal by combining next generation sequencing with new proteomics methods developed by our group. Next, we will synthesize drug-like molecules that can specifically label these tumor-associated proteins. Finally, we will determine how the protein targets of our compounds cause or contribute to cancer. Long-term, our studies will help guide the development of new precision therapies that will have fewer side effects and improved patient outcomes.