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Pancreatic cancer: understanding and overcoming chemoresistance

Nature Reviews Gastroenterology & Hepatology volume 8, pages 27–33 (2011)Cite this article

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Abstract

Pancreatic cancer is a highly aggressive malignancy. This feature is believed to be partly attributable to the chemotherapy-resistant characteristics of specific subgroups of pancreatic cancer cells, namely those with an epithelial–mesenchymal transition (EMT) phenotype and cancer stem cells. Accumulating evidence suggests that several new and emerging concepts might be important in the drug-resistant phenotype of these cell types. An understanding of the molecular mechanisms underlying drug resistance in patients with pancreatic cancer might help researchers to devise novel strategies to overcome such resistance. In particular, microRNAs (miRNAs) seem to be critical regulators of drug resistance in pancreatic cancer cells. Selective and targeted elimination of cells with an EMT phenotype and cancer stem cells could be achieved by regulating the expression of specific miRNAs.

Key Points

  • Cells with an epithelial–mesenchymal transition (EMT) phenotype, cancer stem cells and specific microRNAs (miRNAs) are critical mediators of drug resistance in patients with pancreatic cancer

  • Understanding the mechanisms underlying drug resistance should help researchers to devise novel treatment strategies for patients with pancreatic cancer

  • Selective, targeted elimination of cells with an EMT phenotype and cancer stem cells could potentially increase drug sensitivity and thus improve patients' responses to treatment

  • Natural agents could potentially be included in combination therapies to regulate miRNAs, reverse the EMT phenotype and eliminate cancer stem cells that are resistant to drugs

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Figure 1: Schematic diagram of the EMT.
Figure 2: Production of miRNA and its effect on gene expression.
Figure 3: The links between cells that have an EMT phenotype, cancer stem cells, miRNAs and drug resistance.

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Authors and Affiliations

  1. Department of Pathology, Karmanos Cancer Institute, Wayne State University, School of Medicine, 740 Hudson-Webber Cancer Research Center, 4100 John R. Street, Detroit, 48201, MI, USA

    Zhiwei Wang, Yiwei Li, Aamir Ahmad, Sanjeev Banerjee, Asfar S. Azmi, Dejuan Kong & Fazlul H. Sarkar

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  1. Zhiwei Wang
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Contributions

F. H. Sarkar, Z. Wang and Y. Li researched data for the article. F. H. Sarkar, Z. Wang, A. Ahmad, S. Banerjee and D. Kong contributed to discussion of the content. F. H. Sarkar, Z. Wang, Y. Li, A. S. Azmi and D. Kong wrote the article. F. H. Sarkar, Z. Wang, Y. Li, A. Ahmad, S. Banerjee and A. S. Azmi reviewed and edited the manuscript before submission.

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Correspondence to Fazlul H. Sarkar.

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Wang, Z., Li, Y., Ahmad, A. et al. Pancreatic cancer: understanding and overcoming chemoresistance. Nat Rev Gastroenterol Hepatol 8, 27–33 (2011). https://doi.org/10.1038/nrgastro.2010.188

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