**1. Introduction**

With an increasing incidence each year, cancer represents a major health problem worldwide, ranked second, after cardiovascular disease. According to the last estimation presented by the International Agency for Research on Cancer (IARC) in 2012, more than 14 million new cases of cancers were encountered, while the cancer-related deaths reached around 8.2 million people [1]. Unfortunately, the estimation for 2030 shows an increase in over 21 million new cancer cases and about 13 million cancer deaths [2]. Cancer is characterized by changing the phenotype of the cells in which it occurs, leading to an uncontrolled proliferation, invasion, and metastasis. Albeit the cancers in early stages are treatable, especially by surgery, the major challenge is to treat cancers in advanced stages. Currently, the therapeutic regimens for treating the advanced cancers depend on several factors such as localization, phenotype, and tumor size and are based on a combination of at least two of more approaches, represented by surgery, chemotherapy, radiotherapy, hormone therapy, and target therapy. Nevertheless, this anticancer armamentarium is not very efficient because about 90% of advanced cancers lead to metastasis and death ultimately [3]. Current anticancer therapies target either antiproliferative or proapoptotic pathways of tumor cells or activate immune response against tumors, but

none of the currently available antitumor therapies target the molecular pathways involved in invasion and metastasis.

Tumor invasion and metastasis, as they were pointed out by Hanahan and Weinberg [4], represent one of the most important hallmarks of cancer, and therefore, exploiting these features of tumor cells could bring new data to develop more powerful anticancer therapies. Tumor invasion and metastasis are very complex processes that involve a series of sequential and interrelated steps. In this line, epithelial-to-mesenchymal transition (EMT) represents the most important event underlying the tumor invasion [5]. During EMT, tumor cells lose their epithelial characteristics and adhesion and acquire increased motility by shifting toward a mesenchymal phenotype while also diminishing apoptosis and senescence and gaining stem cell properties. The EMT regulation includes a network of many regulators, inducers, and effector molecules, which sustains tumor cell dissemination to distant organs [6].

The "omics" revolution has brought us new data about the complexity of signaling pathways in cancer, the type of molecules that are involved in them, and which alterations are associated with cancer. Moreover, noncoding RNAs, including miR-NAs, have proved their crucial role in the regulation of mRNA translation in both physiological and pathological status. Because of their high capacity to modulate mRNA expression, miRNAs are defined as master modulators of the human genome. Therefore, miRNAs are involved in all cancer hallmarks, disrupting the normal function of their targets. By gaining or losing the function, miRNAs lead to the validation of tumor phenotype, its progression, and metastasis as well as to drug resistance.

Increasing the evidence suggests that the modulation of miRNA expression in cancer cells, through the inhibition of oncogenic miRNAs (oncomiRs) and the substitution of deficient tumor suppressive miRNAs (TS-miRNAs), could represent a reliable tool for improving the cancer therapy. In this chapter, we will present an up-to-date overview about the role of miRNA-based therapeutics in oncology, highlighting their role in cancer management, how these therapies can be used, and which would be the future challenges related to miRNA-based therapies.
