marizomib and Central-Nervous-System-Neoplasms

Bortezomib was the first proteasome inhibitor (PI) discovered and demonstrated great efficacy in myeloma, both in vitro and in patients. However, still many patients ultimately relapse and there is the need for novel therapies. A second generation of PI have been discovered, potentially more effective ands some also orally administered. Carfilzomib is an irreversible proteasome inhibitor that showed great efficacy in clinical studies. Ixazomib is an oral compound that has been introduced recently in the therapeutic spectrum. Novel agents such as Marizomib seem promising in the fact that can also pass through the blood brain barrier and maybe effective also in CNS muyeloma. This review focus on all proteasome inhibitors available in clinics and the new ones coming soon.

Topics: Animals; Boronic Acids; Bortezomib; Central Nervous System Neoplasms; Drug Discovery; Humans; Lactones; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides; Proteasome Inhibitors; Pyrroles; Threonine

Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed-refractory multiple myeloma (RRMM) and malignant glioma. Central nervous system-multiple myeloma (CNS-MM) is a rare manifestation of extra-medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS-MM therapeutic intervention. Herein, we present two patients with RRMM and CNS involvement who benefited from marizomib-based therapy. These cases provide the first proof of principle for further exploring marizomib in CNS-MM patients.

Topics: Adult; Central Nervous System Neoplasms; Humans; Lactones; Male; Middle Aged; Multiple Myeloma; Pyrroles