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Role of cancer stem cells in pancreatic ductal adenocarcinoma

Nature Reviews Clinical Oncology volume 6, pages 580–586 (2009)Cite this article

Abstract

As our understanding of pancreatic cancer evolves, evidence is growing to support a role for cancer stem cells in this devastating disease. Cancer stem cells constitute a distinct subpopulation in the tumor and are considered to drive both tumorigenesis and metastasis; these cells are thought to be highly resistant to standard treatment modalities. Here we review the current knowledge on pancreatic cancer stem cells and the implementation of cancer stem cell markers as prognostic or predictive biomarkers. We also discuss prospects for the use of cancer stem cells as targets for future therapeutic regimens in pancreatic cancer.

Key Points

  • Conventional chemotherapy and radiotherapy affect rapidly dividing pancreatic cancer cells but fail to target cancer stem cells that drive tumorigenesis and metastasis

  • Pancreatic cancer stem cells with either a CD44+CD24+ESA+ or a CD133+ phenotype have been identified from primary human pancreatic ductal adenocarcinoma

  • The metastatic potential of pancreatic ductal adenocarcinoma seems to be determined by a subpopulation of CD133+ cells that co-express CXCR4

  • Developmental signaling pathways that regulate self-renewal and cell fate in normal stem cells are also involved in pancreatic cancer stem cells and might serve as novel biomarkers and therapeutic targets

  • Any treatment designed to eradicate pancreatic cancer needs to eliminate all cancer stem cells from the tumor

  • The success of any approach that targets pancreatic cancer stem cells will depend upon further identification and characterization of normal pancreatic stem cells, cancer stem cells and the surrounding tumor stroma

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Figure 1: FACS dot plot of a fresh human PDAC specimen.
Figure 2: Model of conventional versus CSC-targeting therapy.

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Acknowledgements

The authors gratefully thank Vik Van Duppen from the Laboratory of Experimental Hematology (SCIL) for sharing his knowledge on fluorescence-activated cell sorting, and Herlinda Vekemans from the ILT (K. U. Leuven) for medical English proofreading of this manuscript.

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Authors and Affiliations

  1. Department of Surgery, Catholic University of Leuven, Leuven, Belgium

    Gregory Sergeant

  2. Department of Molecular Cell Biology, Laboratory of Tissue Plasticity, Catholic University of Leuven, Leuven, Belgium

    Hugo Vankelecom & Lies Gremeaux

  3. Department of Surgery, University Hospital of Leuven, Leuven, Belguim

    Baki Topal

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Correspondence to Baki Topal.

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Sergeant, G., Vankelecom, H., Gremeaux, L. et al. Role of cancer stem cells in pancreatic ductal adenocarcinoma. Nat Rev Clin Oncol 6, 580–586 (2009). https://doi.org/10.1038/nrclinonc.2009.127

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