Aberrant signaling pathways in pancreatic cancer: a two compartment view

Mol Carcinog. 2012 Jan;51(1):25-39. doi: 10.1002/mc.20827.

Abstract

Pancreatic cancer is a devastating disease with historically limited success in treatment and a poor prognosis. Pancreatic cancer appears to have a progressive pathway of development, initiating from well-described pancreatic intraepithelial neoplasia lesions and concluding with invasive carcinoma. These early lesions have been shown to harbor-specific alterations in signaling pathways that remain throughout this tumorigenesis process. Meanwhile, new alterations occur during this process of disease progression to have a cumulative effect. This series of events not only impacts the epithelial cells comprising the tumor, but they may also affect the surrounding stromal cells. The result is the formation of complex signaling networks of communication between the tumor epithelial cell and the stromal cell compartments to promote a permissive and cooperative environment. This article highlights some of the most common pathway aberrations involved with this disease, and how these may subsequently affect one or both cellular compartments. Consequently, furthering our understanding of these pathways in terms of their function on the tumoral epithelial and stromal compartments may prove to be crucial to the development of targeted and more successful therapies in the future.

Trial registration: ClinicalTrials.gov NCT00844649.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Cell Communication
  • Clinical Trials as Topic
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Genes, p16
  • Genes, p53
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / genetics
  • Humans
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptors, Notch / genetics
  • Signal Transduction / genetics*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transforming Growth Factor beta / genetics
  • Wnt Proteins / genetics
  • ras Proteins / genetics

Substances

  • Hedgehog Proteins
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Receptors, Notch
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins

Associated data

  • ClinicalTrials.gov/NCT00844649