The Pancreas Cancer Microenvironment

• Published in: Clinical cancer research Vol. 18; no. 16; pp. 4266 - 4276
• Main Authors: FEIG, Christine, GOPINATHAN, Aarthi, NEESSE, Albrecht, CHAN, Derek S, COOK, Natalie, TUVESON, David A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-08-2012
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - pathology; Extracellular Matrix; Fibroblasts; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hypoxia; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pancreatic Stellate Cells; Pharmacology. Drug treatments; Stromal Cells; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumors; Digestive diseases; Malignant tumor; Microenvironment; Pancreas cancer; Cancer; Pancreatic disease
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-11-3114

Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients.