title: Pancreatic Cancer Genomes: Implications for Clinical Management and Therapeutic Development.
abstract: Pancreatic cancer has become the third leading cause of cancer-related death, with little improvement in outcomes despite decades of research. Surgery remains the only chance of cure, yet only 20% of patients will be alive at 5 years after pancreatic resection. Few chemotherapeutics provide any improvement in outcome, and even then, for approved therapies, the survival benefits are marginal. Genomic sequencing studies of pancreatic cancer have revealed a small set of consistent mutations found in most pancreatic cancers and beyond that, a low prevalence for targetable mutations. This may explain the failure of conventional clinical trial designs to show any meaningful survival benefit, except in small and undefined patient subgroups. With the development of next-generation sequencing technology, genomic sequencing and analysis can be performed in a clinically meaningful turnaround time. This can identify therapeutic targets in individual patients and personalize treatment selection. Incorporating preclinical discovery and molecularly guided therapy into clinical trial design has the potential to significantly improve outcomes in this lethal malignancy. In this review, we discuss the findings of recent large-scale genomic sequencing projects in pancreatic cancer and the potential relevance of these data to therapeutic development.Clin Cancer Res; 23(7); 1638-46. ©2017 AACRSee all articles in thisCCR Focussection, "Pancreatic Cancer: Challenge and Inspiration."
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, United Kingdom.|West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Dreyer
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, United Kingdom.|West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: David K
authors.initials: DK
authors.lastname: Chang
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Bailey
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, United Kingdom. Andrew.Biankin@glasgow.ac.uk.|West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.|South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales, Australia.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
mesh_terms: D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018579:Patient Selection; D057285:Precision Medicine