Grant: Project Grant

Lung cancer is a leading cause of cancer mortality, with a five-year survival rate of 15%. Most cases are non-small cell lung cancer (NSCLC), many involving mutation of an important membrane protein called the Epidermal Growth Factor Receptor (EGFR). While several drugs have been developed to help treat NSCLC associated with mutated EGFR, their effectiveness has been limited by the development of new mutants that resist the drug treatment. Additionally, there are mutants of EGFR-associated NSCLC for which no effective drugs are yet available. Therefore, there is an urgent need to develop new medicines which can be used against these deadly forms of cancer. Recently we developed a new assay, MaMTH-DS, which can be used to quickly identify drugs targeting a variety of different diseases, including cancer. Using this assay we were able to detect a new compound, 5213777, which displays strong activity against a common form of EGFR-associated NSCLC that is resistant to all currently available drugs. In this proposal, we seek to further study compound 5213777, and closely related molecules, to better understand how they work against NSCLC and to determine if they can be adapted for use as new chemotherapeutic agents. Additionally, we seek to apply our MaMTH-DS assay to find new drugs targeting NSCLC, involving mutant forms of EGFR, for which no specific treatment options currently exist.