The pancreatic cancer microenvironment: A true double agent

J Surg Oncol. 2017 Jul;116(1):7-15. doi: 10.1002/jso.24643. Epub 2017 Jun 12.

Abstract

The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed.

Keywords: focal adhesion kinase; hedgehog inhibitors; hyaluronan; immunotherapy; tumor microenvironment; vitamin D.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Angiogenesis Inhibitors / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer-Associated Fibroblasts / pathology
  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • Clinical Trials as Topic
  • Connective Tissue Growth Factor / antagonists & inhibitors
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors
  • Hedgehog Proteins / antagonists & inhibitors
  • Humans
  • Hyaluronic Acid / metabolism
  • Immunotherapy
  • Macrophages / pathology
  • Myeloid Cells / pathology
  • Neutrophils / pathology
  • Osteonectin / antagonists & inhibitors
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Stellate Cells / pathology
  • Tumor Microenvironment*
  • Vitamin D / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Angiotensin II Type 1 Receptor Blockers
  • Hedgehog Proteins
  • Osteonectin
  • SPARC protein, human
  • Connective Tissue Growth Factor
  • Vitamin D
  • Hyaluronic Acid
  • Focal Adhesion Protein-Tyrosine Kinases