title: Pancreatic cancer.
abstract: Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.
authors.affiliation: NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.|Department of General, Visceral and Pediatric Surgery, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Jorg
authors.initials: J
authors.lastname: Kleeff
authors.affiliation: Departments of Medicine, and Biochemistry and Molecular Biology, Indiana University School of Medicine, the Melvin and Bren Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indianapolis, Indiana, USA.
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.affiliation: SWS Clinical School, University of New South Wales, and Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia.
authors.forename: Minoti
authors.initials: M
authors.lastname: Apte
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.affiliation: University Surgical Unit, University Hospital Southampton, Southampton, UK.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Johnson
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, UK.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Neale
authors.affiliation: UCSF Pancreas Center, University of California San Francisco - Mission Bay Campus/Mission Hall, San Francisco, California, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Tempero
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Tuveson
authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D003920:Diabetes Mellitus / Q000209:etiology; D055088:Early Detection of Cancer / Q000592:standards; D006801:Humans; D007565:Jaundice / Q000209:etiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D023421:Models, Animal; D009363:Neoplasm Proteins / Q000032:analysis / Q000097:blood; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000097:blood; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D015431:Weight Loss / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009363:Neoplasm Proteins; C029664:cancer basic protein, human; D016283:Proto-Oncogene Proteins p21(ras)