MicroRNAs as new therapeutic targets and tools in cancer

Introduction: MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs that negatively regulate gene expression at the post-transcriptional level. Several studies have provided evidence that abnormal expression of selected miRNAs is associated with the pathogenesis of cancer. As they can act as either oncogenes or tumor suppressors, miRNAs have been proposed as potential new therapeutic targets or tools for cancer therapy. Areas covered: This paper reviews a significant body of the experimental data collected to date which indicate that specific miRNA inhibition or replacement can successfully modify the proliferative and invasive properties of tumor cells. It discusses recent evidence that has also revealed a direct involvement of miRNAs in drug resistance, underlying an entirely new mechanism by which tumor cells may be refractory to the treatment with cytotoxic agents. Based on these findings, in the therapeutic setting, interference with cancer-specific miRNAs could be exploited not only to produce a direct anticancer effect but also to improve the response of tumor cells to conventional treatments. Expert opinion: Overall, manipulation of miRNA functions, either by mimicking or inhibiting them, is emerging as a highly promising therapeutic strategy. However, before miRNA-based therapeutics enters the clinical armamentarium, important issues concerning specific delivery to cells/tissues of interest, safety as well as pharmacokinetic profiles needs to be addressed.