Targeting Aggressive Fibroblasts to Enhance the Treatment of Pancreatic Cancer

Yuanyuan Yu, Kathleen Schuck, Helmut Friess, Bo Kong

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancer entities, which is characterized by abundant desmoplastic stroma. The stroma consists of extracellular matrix, infiltrating immune cells, cancer-associated fibroblasts (CAFs) and others. Depending on environmental cues, CAFs can be highly heterogeneous and play context-dependent roles in PDAC progression. Areas covered: In this article, we discuss the biological significance of CAFs heterogeneity (oncogenic vs. tumor-suppressive) in pancreatic carcinogenesis. In particular, the complex interaction between CAFs and infiltrating immune cells has a determinant role in defining the stromal composition. A subset of PDAC patients may benefit from anti-CAFs therapy. Expert opinion: Co-defined by CAFs and infiltrating immune cells, the prognostic stroma signature is clinically relevant in a subset of human PDAC. This is the patient population which may benefit from future anti-stroma or anti-CAFs therapies. To consider CAF heterogeneity is crucial for designing anti-stroma studies. Here, reliable and traceable subtype-specific markers for CAFs are urgently needed to dissect the biological impact of CAF heterogeneity on PDAC development spatiotemporally. Given the significant contribution of CAFs to immunosuppressive microenvironment of PDAC, it is conceivable to combine anti-CAFs therapy with immunotherapy. To implement a CAF-subtype specific therapy is crucially important to improve the effectiveness of current treatments including chemotherapies and immunotherapy.

Original languageEnglish
Pages (from-to)5-13
Number of pages9
JournalExpert Opinion on Therapeutic Targets
Volume25
Issue number1
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • CAF
  • CAF heterogeneity
  • PSC
  • Pancreatic cancer
  • desmoplastic reaction

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