miRNA- and lncRNA-Based Therapeutics for Non-Hodgkin's Lymphoma: Moving towards an RNA-Guided Precision Medicine.

Increasing evidence has demonstrated the functional roles of miRNAs and lncRNAs in lymphoma onset and progression, either by acting as tumor-promoting ncRNAs or as tumor suppressors, emphasizing their appeal as lymphoma therapeutics. In fact, their intrinsic ability to modulate multiple dysregulated genes and/or signaling pathways makes them an attractive therapeutic approach for a multifactorial pathology like lymphoma. Currently, the clinical application of miRNA- and lncRNA-based therapies still faces obstacles regarding effective delivery systems, off-target effects, and safety, which can be minimized with the appropriate chemical modifications and the development of tumor site-specific delivery approaches. Moreover, miRNA- and lncRNA-based therapeutics are being studied not only as monotherapies but also as complements of standard treatment regimens to provide a synergic effect, improving the overall treatment efficacy and reducing the therapeutic resistance. In this review, we summarize the fundamentals of miRNA- and lncRNA-based therapeutics by discussing the different types of delivery systems, with a focus on those that have been investigated in lymphoma in vitro and in vivo. Moreover, we described the ongoing clinical trials of novel miRNA- and lncRNA-based therapeutics in lymphoma.