LAUSR

Simple Summary Over the last few years, we have witnessed incredible advancements in anti-tumor drug development. microRNAs, a class of small non-coding RNAs dysregulated in all cancers, have been recently elected as candidate therapeutics for treating a variety of diseases, including cancer. The scope of this review is to give some insight into the role of the most relevant microRNAs in cancer. We will focus on examining their biological role in tumor development while also providing a broad overview of microRNAs as therapeutics. There is a dedicated focus on the different methods available for microRNA delivery in addition to the efforts being made to increase the specificity of these delivery methods. Finally, we discuss the ongoing clinical trials that are using microRNAs for cancer treatment. Abstract In the last 20 years, the functional roles for miRNAs in gene regulation have been well established. MiRNAs act as regulators in virtually all biological pathways and thus have been implicated in numerous diseases, including cancer. They are particularly relevant in regulating the basic hallmarks of cancer, including apoptosis, proliferation, migration, and invasion. Despite the substantial progress made in identifying the molecular mechanisms driving the deregulation of miRNAs in cancer, the clinical translation of these important molecules to therapy remains in its infancy. The paucity of vehicles available for the safe and efficient delivery of miRNAs and ongoing concerns for toxicity remain major obstacles to clinical application. Novel formulations and the development of new vectors have significantly improved the stability of oligonucleotides, increasing the effectiveness of therapy. Furthermore, the use of specific moieties for delivery in target tissues or cells has increased the specificity of treatment. The use of new technologies has allowed small but important steps toward more specific therapeutic delivery in tumor tissues and cells. Although a long road remains, the path ahead holds great potential. Currently, a few miRNA drugs are under investigation in human clinical trials with promising results ahead.