MiRNAs and Their Interference with the Main Molecular Mechanisms Responsible for Drug Resistance in Pancreatic Cancer

Garajová I, Giovannetti E, Caponi S, van Zweeden A, Peters GJ.

Curr Pharmacol Rep (2015) 1:223–233


Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous disease with a very limited re- sponse to most treatments. The main mechanisms responsible for drug resistance in PDAC include molecular aberrations in key regulatory genes or signaling pathways, the desmoplastic reaction which characterize pancreatic cancer microenvironment, and the presence of resistant cancer stem cells (CSCs). The recent discovery of microRNAs (miRNAs) provided new directions for re- search on all these mechanisms, demonstrating their important role in the regulation of many important biological processes, such as cell survival, proliferation, migration, invasion, and metastasis. Furthermore, there is in- creasing interest in defining a functional association be- tween miRNAs and chemoresistance, with the double aim to rationally design miRNA-based strategies to improve clinical outcome and to identify novel biomarkers of treat- ment response. In this review, we summarize the current knowledge on the role of miRNAs and their interference with the main molecular mechanisms responsible for drug resistance in PDAC.

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