At preclinical level, several siRNA- or shRNA-based tools have successfully reversed Dox resistance in osteosarcoma, e.g., by directly silencing Pgp [59,60] or by silencing transcription factors, as estrogen-related receptor α (ERRα) that up-regulates Pgp [61] or nuclear factor (erythroid-derived 2)-like 2 (NRF2) that mediates resistance to oxidative stress and up-regulates multiple ABC transporters [62]. This evidence concerns the gene ESRRA and osteosarcoma.