Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma

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Authors

KUBICZKOVÁ Lenka POUR Luděk SEDLAŘÍKOVÁ Lenka HÁJEK Roman ŠEVČÍKOVÁ Sabina

Year of publication 2014
Type Article in Periodical
Magazine / Source Journal of Cellular and Molecular Medicine
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1111/jcmm.12279
Field Oncology and hematology
Keywords Bortezomib; Multiple myeloma; New-generation proteasome inhibitors
Description Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second-generation PI oprozomib is being investigated. This review provides an overview of main mechanisms of action of PIs in MM, focusing on the ongoing development and progress of novel anti-proteasome therapeutics.
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