The proteasome-regulating kinase DYRK2 as a target in breast cancer and multiple myeloma
INDICATION: Breast cancer; multiple myeloma (MM)
Inhibiting the proteasome-regulating kinase DYRK2 could treat breast cancer and MM. In patients with triple-negative breast cancer (TNBC) or MM, DYRK2 expression and protein levels were higher in tumor samples than in matched samples of normal tissue. In two mouse MM cell lines, DYRK2 knockout decreased proliferation. Tumor-specific DYRK2 knockout reduced tumor growth in a xenograft mouse model of TNBC and extended survival in a syngeneic mouse model of MM. In the MM model, a DYRK2 inhibitor tool compound reduced tumor volume and signs of MM-associated bone degeneration and improved mean survival from 19 to 28.5 days. In both a xenograft mouse model of MM resistant to the marketed MM drug Velcade bortezomib and a patient-derived xenograft (PDX) mouse model of TNBC, the DYRK2 inhibitor reduced tumor growth...