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Targeted Oncology
Published in: Targeted Oncology 6/2020

01-12-2020 | Multiple Myeloma | Review Article

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy

Authors: Nicholas Theodoropoulos, Guido Lancman, Ajai Chari

Published in: Targeted Oncology | Issue 6/2020

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Abstract

Multiple myeloma (MM) is an incurable malignancy of plasma cells with a clinical course characterized by multiple relapses and treatment refractoriness. While recent treatment advancements have extended overall survival (OS), refractory MM has a poor prognosis, with a median OS of between 4 and 6 months. Nuclear export inhibition, specifically inhibition of CRM1/XPO1, is an emerging novel treatment modality that has shown promise in treatment-refractory MM. Initially discovered in yeast in 1983, early clinical applications were met with significant toxicities that limited their utility. The creation of small molecule inhibitors of nuclear export (SINE) has improved on toxicity limitations and has led to investigation in a number of malignancies at the preclinical and clinical stages. Preclinical studies of SINEs in MM have shown that these molecules are cytotoxic to myeloma cells, play a role in therapy resensitization, and suggest a role in limiting bone disease progression. In July 2019, selinexor became the first nuclear export inhibitor approved for use in relapsed/refractory MM based on the STORM trial. As of May 2020, there were eight ongoing trials combining selinexor with standard treatment regimens in relapsed/refractory MM. Eltanexor, a second-generation SINE, is also under investigation and has shown preliminary signs of efficacy in an early clinical trial while potentially having an improved toxicity profile compared with selinexor. Results in ongoing trials will help further define the role of SINEs in MM.
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Metadata
Title
Targeting Nuclear Export Proteins in Multiple Myeloma Therapy
Authors
Nicholas Theodoropoulos
Guido Lancman
Ajai Chari
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 6/2020
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-020-00758-2

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