Non-coding RNAs, including small interfering RNAs (siRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are gaining prominence in clinical medicine as potential diagnostics and therapeutics. In addition, given that some of these ncRNAs can be efficiently transferred between cells via extracellular vesicles (EVs), they can also have “hormone-like” effects acting at a distance from their secretory cells (eg. miR-221/222 in mediating resistance to tamoxifen). We have previously identified and characterised several novel nuclear receptor coregulators (SLIRP, PACT, TRBP) that bind SRA, a lncRNA, and regulate hormone action (oestrogen and androgen) in breast and prostate cancer, respectively. In addition, we have characterised several miRNAs that inhibit androgen action and prostate cancer tumourigenesis. With the introduction of 2nd generation synthetic chemistry, the stability of short double stranded RNAs (dsRNAs, siRNAs and miRNAs) has been dramatically enhanced, producing profound effects on target gene expression, and leading to the FDA approval in late 2018 of the first siRNA drug, Patisiran. This landmark decision paves the way for subsequent dsRNA drug development. We have applied 2nd generation synthetic chemistry to develop a novel miRNA mimic for the treatment of epithelial cancers. In addition, we have engineered a liver-specific version of the miRNA mimic to treat hepatocellular carcinoma (HCC). The application of these emerging technologies to the treatment of endocrine and liver cancer will be discussed.