Pancreatic neuroendocrine tumours are the second most common malignancy of the pancreas with a five-year survival rate of approximately 40%. Patients are often diagnosed with extensive metastasis and therefore must embark on a severe chemotherapeutic regimen that showed limited efficacy. There is a need for novel systemic therapies and this past week (Feb 10, 2011) brought exciting news:

The compound Everolimus was just reported to significantly increase the progression-free survival of patients affected with pancreatic neuroendocrine tumours. Everolimus acts by shutting down a molecular pathway that is often found hyperactivated in pancreatic neuroendocrine tumours, the mTOR pathway. This past year, several novel second-generation inhibitors of mTOR were discovered, and they demonstrated a much higher efficacy in inhibiting this pathway as well as greater anti-cancer properties.

Our goal is to assess the novel active-site inhibitors of mTOR in pancreatic neuroendocrine tumours. By using a biochemical, genetic, and animal model approach, we aim to elucidate the mechanisms by which mTOR, and its downstream effectors, regulate neuroendocrine tumour progression. Furthermore, we will identify novel biomarkers that act on this disease and predict response to therapeutic inhibition of the mTOR pathway. Our study will provide insightful information for the treatment of pancreatic neuroendocrine tumors using mTOR inhibitor compounds.

This grant is jointly funded by CNETS (Carcinoid NeuroEndocrine Tumor Society of Canada) and the Cancer Research Society.