Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma therapy: Challenges and opportunities

Qin Qin, Rong Yu, John E. Eriksson, Hsiang i. Tsai*, Haitao Zhu*

*Corresponding author for this work

Research output: Contribution to journalReview Article or Literature Reviewpeer-review

14 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a solid organ malignancy with a high mortality rate. Statistics indicate that its incidence has been increasing as well as the associated deaths. Most patients with PDAC show poor response to therapies making the clinical management of this cancer difficult. Stromal cells in the tumor microenvironment (TME) contribute to the development of resistance to therapy in PDAC cancer cells. Cancer-associated fibroblasts (CAFs), the most prevalent stromal cells in the TME, promote a desmoplastic response, produce extracellular matrix proteins and cytokines, and directly influence the biological behavior of cancer cells. These multifaceted effects make it difficult to eradicate tumor cells from the body. As a result, CAF-targeting synergistic therapeutic strategies have gained increasing attention in recent years. However, due to the substantial heterogeneity in CAF origin, definition, and function, as well as high plasticity, majority of the available CAF-targeting therapeutic approaches are not effective, and in some cases, they exacerbate disease progression. This review primarily elucidates on the effect of CAFs on therapeutic efficiency of various treatment modalities, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Strategies for CAF targeting therapies are also discussed.

Original languageEnglish
Article number216859
JournalCancer Letters
Volume591
DOIs
Publication statusPublished - 1 Jun 2024
MoE publication typeA2 Review article in a scientific journal

Keywords

  • Cancer-associated fibroblasts
  • Heterogeneity
  • Pancreatic ductal adenocarcinoma
  • Therapy resistance
  • Tumor microenvironment

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