Translational advances and novel therapies for pancreatic ductal adenocarcinoma: hope or hype?

Biological complexity, inaccessible anatomical location, nonspecific symptoms, lack of a screening biomarker, advanced disease at presentation and drug resistance epitomise pancreatic ductal adenocarcinoma (PDA) as a poor-prognosis, lethal disease. Twenty-five years of research (basic, translational and clinical) have barely made strides to improve survival, mainly because of a fundamental lack of knowledge of the biological processes initiating and propagating PDA. However, isolation of pancreas cancer stem cells or progenitors, whole-genome sequencing for driver mutations, advances in functional imaging, mechanistic dissection of the desmoplastic reaction and novel targeted therapies are likely to shed light on how best to treat PDA. Here we summarise current knowledge and areas where the field is advancing, and give our opinion on the research direction the field should be focusing on to better deliver promising therapies for our patients.