NEK2 is a drug resistance-inducing protein accumulated in the blood cancer Myeloma however, the mechanism is unknown. My dissertation shows NEK2 is stabilized by interacting with USP7, another cancer-promoting protein. Once stable, my data shows NEK2 promotes drug resistance by activating NF-kB, a pro-survival pathway. Furthermore, inhibiting NEK2, NF-kb or USP7 overcomes drug resistance mediated by NEK2 in cell lines and mouse models, suggesting NEK2 is an attractive therapeutic target for Myeloma patients.