Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

Gut. 2019 Jan;68(1):159-171. doi: 10.1136/gutjnl-2018-316451. Epub 2018 Sep 3.

Abstract

Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.

Keywords: molecular carcinogenesis; molecular mechanisms; molecular oncology; pancreatic cancer; pancreatic fibrosis.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / therapy*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Disease Progression
  • Forecasting
  • Humans
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / therapy*
  • Prognosis
  • Signal Transduction
  • Stromal Cells / pathology*
  • Translational Research, Biomedical
  • Tumor Microenvironment / physiology*

Substances

  • Antineoplastic Agents