TAK1-inhibitors did not reduce disease burden in a Vκ*MYC model of multiple myeloma

Abstract

Abstract Objective Multiple myeloma is a haematological malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Development of resistance and minimal residual disease remain challenging in the treatment of multiple myeloma. Transforming growth factor-β activated kinase 1 (TAK1) has recently gained attention as a potential drug target in multiple myeloma. This study aimed at determining the in vivo effects of TAK1-inhibitors in a Vκ*MYC multiple myeloma mouse model. Results We treated mice carrying Vκ*MYC multiple myeloma cells with the TAK1-inhibitors 5Z-7-oxozeaenol and NG25. There were tendencies towards increased survival for both inhibitors, but only NG25 prolonged survival significantly. However, this effect was limited, and no differences in disease burden were observed for any of the treatments. In conclusion, although TAK1-inhibitors might prolong survival somewhat, they do not prevent disease in the Vκ*MYC mouse model of multiple myeloma.

Keywords

• Multiple myeloma
• TAK1
• Haematological malignancy
• 5Z-7
• NG25