Grant: Project Grant

Lung cancer is the leading cause of cancer mortality worldwide, suffering from a late stage of disease at the time of diagnosis and a paucity of effective drugs available to treat advanced tumours. Despite a greater understanding of the genetic basis of lung cancer development, discovery of new therapeutics has been slow as the activities of genes implicated in this disease are difficult to inhibit while new agents targeting lung cancer cells have been ineffective due to drug resistance. Therefore, new strategies are urgently needed to develop effective therapeutic strategies for lung cancer patient therapy that yield robust responses and improve long-term survival rates. The current approach to drug discovery mainly entails identifying a gene that is mutated in lung tumours, determining if its modulation impacts cancer growth and then screening or designing drugs to inhibit gene function. An alternative approach would be to use information about what genes are never activated in lung tumours to uncover potential avenues for therapeutic intervention. The idea is that the reason these genes are not activated in lung tumours is because they were incompatible with cancer growth. With this in mind, we assessed lung tumours from over 600 patients and discovered two genes that were never activated together. When we engineered lung cancer cells to have activation of both of these genes, we found that the cancer cells died in robust fashion. The goal of this proposal is to understand why co-activation of these two genes kills cancer cells and determine whether drugs that can mimic this scenario offer an effective way of inhibiting lung tumour growth. We also aim to test candidate drugs in mice that develop lung cancer to gain insight regarding their potential use in the treatment of human patients. Thus, this work will offer true progress towards developing new agents for the treatment of lung cancer, ultimately leading to improved survival rates for patients.