[Proteasome inhibitors in treatment of multiple myeloma]

Multiple myeloma, a plasma cell malignancy, still remains a hard-to-treat hematological disease that desperately needs new therapy targeting plasmocytes but also the bone marrow microenvironment. Clonal plasmocytes are characterized by increased regulation of ubiquitin-proteasome pathway which augments their sensitivity to proteasome inhibitors. Treatment strategies based on proteasome inhibitors belong to the era of new drugs, and they have become increasingly important for treatment of multiple myeloma in recent years. Bortezomib became the first proteasome inhibitor approved for the treatment of multiple myeloma and showed remarkable anti-myeloma activity. However, despite its high efficiency, a large proportion of patients have became bortezomib resistant. The second generation of proteasome inhibitors - carfilzomib, marizomib and MLN9708 - were developed in an effort to overcome bortezomib-resistance and find proteasome inhibitors with a better toxic profile. These drugs brought a chance that multiple myeloma would become a chronic disease.