New biomarkers and targets in pancreatic cancer and their application to treatment

Nat Rev Gastroenterol Hepatol. 2012 Aug;9(8):435-44. doi: 10.1038/nrgastro.2012.119. Epub 2012 Jun 26.

Abstract

Late diagnosis of pancreatic ductal adenocarcinoma (pancreatic cancer) and the limited response to current treatments results in an exceptionally poor prognosis. Advances in our understanding of the molecular events underpinning pancreatic cancer development and metastasis offer the hope of tangible benefits for patients. In-depth mutational analyses have shed light on the genetic abnormalities in pancreatic cancer, providing potential treatment targets. New biological studies in patients and in mouse models have advanced our knowledge of the timing of metastasis of pancreatic cancer, highlighting new directions for the way in which patients are treated. Furthermore, our increasing understanding of the molecular events in tumorigenesis is leading to the identification of biomarkers that enable us to predict response to treatment. A major drawback, however, is the general lack of an adequate systematic approach to advancing the use of biomarkers in cancer drug development, highlighted in a Cancer Biomarkers Collaborative consensus report. In this Review, we summarize the latest insights into the biology of pancreatic cancer, and their repercussions for treatment. We provide an overview of current treatments and, finally, we discuss novel therapeutic approaches, including the role of biomarkers in therapy for pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • CD40 Antigens / physiology
  • Carcinoma in Situ / pathology
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Computational Biology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Drug Therapy, Combination
  • Equilibrative Nucleoside Transport Proteins / blood
  • Fluorouracil / therapeutic use
  • Gene Rearrangement
  • Hedgehog Proteins / physiology
  • Humans
  • MicroRNAs / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Poly(ADP-ribose) Polymerases / drug effects
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / drug effects
  • Signal Transduction / physiology
  • Treatment Outcome
  • ras Proteins / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CD40 Antigens
  • Equilibrative Nucleoside Transport Proteins
  • Hedgehog Proteins
  • KRAS protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Deoxycytidine
  • gemcitabine
  • Poly(ADP-ribose) Polymerases
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Fluorouracil