Pancreatic cancer

Nat Rev Dis Primers. 2016 Apr 21;2:16022. doi: 10.1038/nrdp.2016.22.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified / immunology
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Diabetes Mellitus / etiology
  • Early Detection of Cancer / standards
  • Humans
  • Jaundice / etiology
  • Magnetic Resonance Imaging / methods
  • Mice
  • Models, Animal
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / blood
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / physiopathology*
  • Prognosis*
  • Proto-Oncogene Proteins p21(ras) / analysis
  • Proto-Oncogene Proteins p21(ras) / blood
  • Risk Factors
  • Tomography, X-Ray Computed / methods
  • Weight Loss / immunology

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Neoplasm Proteins
  • cancer basic protein, human
  • Proto-Oncogene Proteins p21(ras)