NOTCHLUNG · Explore novel connections between oncogenic pathways in lung cancer

Lung cancer causes about a million deaths per year and the estimation is that 250 million people will die during the 21st century for this reason. A major challenge in treating this and other cancers is the intrinsic resistance to conventional therapies demonstrated by the cancerous cells that are responsible for the sustained growth, survival, and invasion of the tumour. Identifying new pathways involved in the biological processes necessary for the survival of lung cancerous cells is paramount in developing new clinical approaches with the goal of preventing disease recurrence. Using mouse models, I have recently published as first and corresponding author in the journal Cancer Cell, that non-small cell lung carcinomas (NSCLC) are ""addicted"" to the Notch pathway. Importantly, inhibition of the Notch pathway arrests NSCLC growth in vivo, opening up a new therapeutic approach to the treatment of this disease. My first aim is to develop, in the next few years, a patient-derived tumour xenograft (PDTX) model to extend beyond the realms of rodents the proof of principle of using Notch inhibitors for the treatment of human NSCLC. My second aim will be to identify the different partners and components of the Notch pathway, required for this ""addiction"" and for the maintenance of NSCLC. Finally, using both NSCLC-prone mouse models and the PDTX model I will try to combine therapies currently in use to treat NSCLC with Notch pathway inhibition hoping to identify synergies between these treatments. Of note, the availability and use of a PDTX model will pave the way to personalised treatment of NSCLC patients. My ultimate goal is to find new therapeutic approaches for the treatment of the leading cause of death by Cancer in the world today.""