Developing pancreatic cancer medicines


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David Tuveson
Cancer Research UK, Cambridge, United Kingdom

Abstract

Pancreatic cancer is refractory to current chemotherapy and is responsible for the deaths of over 250,000 patients world-wide per annum.  Explorations of therapeutic response in a Mus Musculus model of pancreatic ductal adenocarcinoma (PDA) have yielded potential mechanisms of disease resistance, and also offer the opportunity to thereby overcome such barriers. 

We recently reported that primary pancreatic ductal adenocarcinoma (PDA) tumours in Mus Musculus and Homo Sapiens contain a deficient and compressed vasculature, and proposed that this may impede effective delivery of chemotherapeutics and other agents with limited bioavailability. Indeed, stromal depletion with a hedgehog pathway inhibitor induced a reactive angiogenesis in the tumour and correspondingly increased chemotherapy delivery and response.  We have now extended our observation to other agents that target neoplastic cells and the tumour microenvironment, and have initiated clinical trials to probe the relevance of such findings in patients.