Currently, combinations of FDA-approved JAK2 inhibitors, including ruxolitinib (Rux) and pacritinib (Pac), and SMO inhibitors including vismodegib (Vis) and sonidegib (Son) exerted synergistic cell kill in a HER2-positive breast cancer cell lines with acquired trastuzumab resistance. The gene discussed is ERBB2; the disease is breast carcinoma.