Differential donor-, cell type- and drug-specific molecular responses to therapeutic proteasome inhibitors in Multiple Myeloma patients and cells

Abstract

Purpose of the study: Proteasome over‐activation represents a hallmark of several advanced tumors and thus, its selective inhibition provides a promising anti‐tumor therapy. Consistently, proteasome inhibitors (PIs) have demonstrated clinical efficacy in the treatment of multiple myeloma (MM) and mantle cell lymphoma and are evaluated for the treatment of other malignancies. Herein we analyzed the molecular responses induced in red blood‐ (RBCs) cells and peripheral blood mononucleated‐ (PBMCs) cells of MM patients treated with therapeutic PIs; given also that disease relapse usually refers to MM cells that survive therapy, we also investigated the molecular responses induced in MM cells after non‐lethal proteasome inhibition.