Unravelling the mechanisms of drug resistance to proteasome inhibitors to optimize treatment in patients with multiple myeloma. (METOYOU)

Although new drug classes were introduced in the past two decades, multiple myeloma (MM) remains an incurable disease. This project aims at improving the treatment of patients with MM by focusing on drug resistance and sensitivity mechanisms to proteasome inhibitors (PIs). We will perform different genome-wide CRISPR-Cas9-based screens on in vitro cultured MM cells. Hits will be validated in patient-derived MM cells. In addition, we will perform a CRISPR mutagenesis screen to map all possible PSMB5 variants conferring resistance to PIs. Finally, a genome-wide CRISPR dropout screen will be performed to identify drug targets that may act synergistically with PIs.