In the current study, we explore the link between DYRK2 and HSF1 further, and query whether dual pharmacological inhibition of DYRK2 and HSF1 could induce enhanced cytotoxicity in proteasome inhibitor resistant cells and whether concurrent inhibition or loss-of-activity of DYRK2 and HSF1 ablates cancer progression. The gene discussed is DYRK2; the disease is cancer.