Grant: Project Grant

Lung cancer is the leading cause of cancer death in Canada and 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 patients that yield robust responses and improve long-term survival rates. Currently, drug discovery is based on identifying mutated genes in lung tumours, determining if its modulation impacts growth, and then screening or designing drugs to inhibit gene function. In this manner, therapies are aimed at "putting the breaks" on the signals that promote tumor growth. Unexpectedly, we have recently found that lung cancer cells also cannot tolerate increases in signaling, akin to "flooring the gas pedal". However, we still do not know why this hyperactive signaling is toxic to cancer cells and whether or not we can use this information to treat cancer patients. The goal of this proposal is to understand why too much signaling kills cancer cells and determine whether drugs that can mimic this scenario offer an effective way of inhibiting lung tumour growth. We aim to test candidate drugs that target the "regulators" in lung cancer cells which act as a fail safe to prevent hyperactivation from occurring. By disrupting these key regulators, we predict that cancer cells will "overheat" from too much signaling, causing their death, and we will assess their effectiveness in model systems for the first time. 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.