Molecular basis of resistance to proteasome inhibitors in hematological malignancies

Over the past decade, the proteasome inhibitor bortezomib (Velcade) has not only gained a cornerstone position in the treatment of hematological malignancies, particularly multiple myeloma and mantle cell lymphoma, but also in experimental therapeutics of acute leukemia. However, the therapeutic efficacy of bortezomib is hampered by the emergence of acquired resistance, for which multifactorial mechanisms have been identified. This review summarizes the current status of the molecular mechanisms underlying resistance to proteasome inhibitors that emerged in preclinical therapeutic studies, and discusses these findings in the clinical perspective of novel therapeutic modalities of hematological malignancies.

Source: Drug Resistance Updates - December 11, 2014 Category: Drugs & Pharmacology Authors: Denise Niewerth, Gerrit Jansen, Yehuda G. Assaraf, Sonja Zweegman, Gertjan L. Kaspers, Jacqueline Cloos Source Type: research