title: Development of Pancreatic Cancer: Targets for Early Detection and Treatment.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death worldwide and compared to other malignancies its share in cancer mortality is expected to rise further. This is due to a lack of sensitive diagnostic tools that would permit earlier detection in a potentially curable stage and the very slow progress in finding effective drug treatments for pancreatic cancer.
  
  
  CONCLUSIONS
  Aside from genetic predispositions and environmental agents, chronic pancreatitis is by far the greatest risk factor for PDAC. It also shares several etiological factors with pancreatic cancer and represents its most challenging differential diagnosis. Biomarkers that can distinguish between chronic pancreatitis and PDAC may therefore be suitable for the latter's early detection. Moreover, targeting the natural history of chronic pancreatitis would be one approach to prevent PDAC. Targeting tumor-cell signaling directly by interfering with receptor tyrosine kinases has shown some efficacy, although the results in clinical trials were less encouraging than for other cancers. Other compounds developed have targeted the formation of extracellular matrix around the tumor, the proteolytic activity in the tumor environment, histone deacetylases, hedgehog signaling and heat shock proteins, but none has yet found its way into routine patient care. Attempts to individualize treatment according to the tumor's somatic mutation profile are novel but so far impractical.
  
  
  CONCLUSIONS
  Progress in the treatment of pancreatic cancer has been exceedingly slow and mostly dependent on improved pharmaceutical preparations or combinations of established chemotherapeutic agents. The promise of major breakthroughs implied in targeting tumor signal transduction events has so far not materialized.
authors.affiliation: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Mahajan
authors.forename: Matthias
authors.initials: M
authors.lastname: Sendler
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Weiss
authors.forename: Ali
authors.initials: A
authors.lastname: Aghdassi
authors.forename: Patryk
authors.initials: P
authors.lastname: Moskwa
authors.forename: Peter
authors.initials: P
authors.lastname: Simon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D050500:Pancreatitis, Chronic / Q000150:complications*; D057285:Precision Medicine / Q000379:methods; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor