Although much work is needed to develop in vivo potent and clinically relevant DYRK2 inhibitors, the work does endorse cotargetting of a kinase and transcription factor as a viable therapeutic option, especially in hard-to-treat breast cancer subtypes and drug-resistant refractory myeloma with a good potential of expanding to other cancers with unmet need. The gene discussed is DYRK2; the disease is plasma cell myeloma.