The impact of miRNAs on resistance to anticancer treatment: The future for miRNA-based targeted therapy?

MicroRNAs (miRNAs, miRs) are naturally occurring, small, non-coding RNA molecules which regulate gene expression at a posttranscriptional level. Since their discovery in the early 1990s, our picture of the complex regulation of global gene expression has changed dramatically. We have learned that epigenetic modulations of gene expression, which are defined as heritable changes in gene expression without alterations of DNA sequences, play an important role in maintaining proper cellular functions. MiRNAs are part of this "epigenetic machinery", and a rapidly increasing number of these molecules had been found in different tissues types across various species. We now know that they are involved in a broad variety of physiological and pathological processes including the pathogenesis and progression of cancer, and, most interestingly, the resistance of various cancers to anticancer treatment. This makes miRNAs interesting possible targets for clinical diagnostic and, even more important, therapeutic applications. With this current review, we provide an overview about the potential role of miRNAs as therapeutic modifiers of chemo-sensitivity in cancer. Therefore, we first outline essential background information on important clinical questions that are linked with aspects of miRNA expression and regulation, their fundamental function in cancer and their detection in different human tissues. Finally, we discuss potential therapeutic strategies based on the modulation of miRNA expression with the focus on their extraordinary role in drug resistance in various human malignancies.