Stromal biology and therapy in pancreatic cancer: a changing paradigm

Gut. 2015 Sep;64(9):1476-84. doi: 10.1136/gutjnl-2015-309304. Epub 2015 May 20.

Abstract

Pancreatic ductal adenocarcinoma (PDA) exhibits one of the poorest prognosis of all solid tumours and poses an unsolved problem in cancer medicine. Despite the recent success of two combination chemotherapies for palliative patients, the modest survival benefits are often traded against significant side effects and a compromised quality of life. Although the molecular events underlying the initiation and progression of PDA have been intensively studied and are increasingly understood, the reasons for the poor therapeutic response are hardly apprehended. One leading hypothesis over the last few years has been that the pronounced tumour microenvironment in PDA not only promotes carcinogenesis and tumour progression but also mediates therapeutic resistance. To this end, targeting of various stromal components and pathways was considered a promising strategy to biochemically and biophysically enhance therapeutic response. However, none of the efforts have yet led to efficacious and approved therapies in patients. Additionally, recent data have shown that tumour-associated fibroblasts may restrain rather than promote tumour growth, reinforcing the need to critically revisit the complexity and complicity of the tumour-stroma with translational implications for future therapy and clinical trial design.

Keywords: PANCREATIC DISEASE; PANCREATIC FIBROSIS; PANCREATIC PATHOLOGY; PANCREATIC TUMOURS; PANCREATITIS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biopsy, Needle
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / physiopathology
  • Forecasting
  • Humans
  • Immunohistochemistry
  • Mice
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / physiopathology
  • Prognosis
  • Stromal Cells / drug effects
  • Stromal Cells / pathology*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / physiology

Substances

  • Antineoplastic Agents