Pancreatic cancer: understanding and overcoming chemoresistance

• Published in: Nature reviews. Gastroenterology & hepatology Vol. 8; no. 1; pp. 27 - 33
• Main Authors: Sarkar, Fazlul H, Wang, Zhiwei, Li, Yiwei, Ahmad, Aamir, Banerjee, Sanjeev, Azmi, Asfar S, Kong, Dejuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2011; Nature Publishing Group
• Subjects: 631/250/2502/2055; 631/80/84/2176; 692/699/67/1059/2326; 692/699/67/1504/1713; Biomedicine; Cancer; Cell Differentiation - physiology; Chemotherapy; Drug Resistance, Neoplasm - physiology; Drug therapy; Epithelial Cells - cytology; Gastroenterology; Genetic aspects; Health aspects; Hepatology; Humans; Medicine; Medicine & Public Health; Mesoderm - cytology; MicroRNAs - physiology; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - physiopathology; review-article; Risk factors; Stem cells; United States
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/nrgastro.2010.188

Pancreatic cancer is a highly aggressive malignancy, which is partly attributable to drug resistance. This Review summarizes the current knowledge of the biological significance of the epithelial–mesenchymal transition, cancer stem cells and microRNAs in the context of drug resistance in patients with pancreatic cancer and describes how this knowledge could be applied to overcoming chemoresistance in pancreatic cancer. 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