Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment

Despite the major advancements in the repertoire for multiple myeloma (MM) treatment, this disease remains a chronically progressive plasma cell malignancy. Drug resistance and high relapse rates complicate the extended treatment strategies. However, the tumor microenvironment (TME) in MM is decisiv...

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Main Authors: Kereshmeh Tasbihi, Heiko Bruns
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/6/430
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author Kereshmeh Tasbihi
Heiko Bruns
author_facet Kereshmeh Tasbihi
Heiko Bruns
author_sort Kereshmeh Tasbihi
collection DOAJ
description Despite the major advancements in the repertoire for multiple myeloma (MM) treatment, this disease remains a chronically progressive plasma cell malignancy. Drug resistance and high relapse rates complicate the extended treatment strategies. However, the tumor microenvironment (TME) in MM is decisive for the success of a therapy or relapse. Aiming to improve the outcome of relapsed and refractory MM patients, Selinexor has entered the drug arsenal of myeloma therapy through the implementation of a novel therapeutic approach by selectively inhibiting the nuclear export receptor Exportin-1 (XPO1). Selinexor leads to the inactivation of cancer-related proteins and induces apoptosis by disrupting the nucleocytoplasmic flow in myeloma cells. While this drug is selectively cytotoxic to neoplastic cells, Selinexor’s immunomodulatory impact on the TME is currently being investigated. The aim of this review was to elucidate Selinexor’s capacity to influence the cell interaction network of the TME from an immunological perspective. Deciphering the complex interplay of highly plastic immune cells provides a contribution to the molecular–biological exploration of disease initiation and progression in MM. Unraveling the novel therapeutic targets of the immunological TME and evaluating the advanced immunotherapeutic regimens implementing Selinexor will shape the future directions of immune-oncotherapy in MM.
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spelling doaj-art-52124205c2794d52a0146760fbb907fa2025-08-20T02:42:35ZengMDPI AGCells2073-44092025-03-0114643010.3390/cells14060430Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma TreatmentKereshmeh Tasbihi0Heiko Bruns1Department of Medicine 5—Hematology and Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Medicine 5—Hematology and Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDespite the major advancements in the repertoire for multiple myeloma (MM) treatment, this disease remains a chronically progressive plasma cell malignancy. Drug resistance and high relapse rates complicate the extended treatment strategies. However, the tumor microenvironment (TME) in MM is decisive for the success of a therapy or relapse. Aiming to improve the outcome of relapsed and refractory MM patients, Selinexor has entered the drug arsenal of myeloma therapy through the implementation of a novel therapeutic approach by selectively inhibiting the nuclear export receptor Exportin-1 (XPO1). Selinexor leads to the inactivation of cancer-related proteins and induces apoptosis by disrupting the nucleocytoplasmic flow in myeloma cells. While this drug is selectively cytotoxic to neoplastic cells, Selinexor’s immunomodulatory impact on the TME is currently being investigated. The aim of this review was to elucidate Selinexor’s capacity to influence the cell interaction network of the TME from an immunological perspective. Deciphering the complex interplay of highly plastic immune cells provides a contribution to the molecular–biological exploration of disease initiation and progression in MM. Unraveling the novel therapeutic targets of the immunological TME and evaluating the advanced immunotherapeutic regimens implementing Selinexor will shape the future directions of immune-oncotherapy in MM.https://www.mdpi.com/2073-4409/14/6/430SelinexorXPOVIOXPO1Exportin-1nuclear exportmultiple myeloma
spellingShingle Kereshmeh Tasbihi
Heiko Bruns
Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
Cells
Selinexor
XPOVIO
XPO1
Exportin-1
nuclear export
multiple myeloma
title Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
title_full Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
title_fullStr Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
title_full_unstemmed Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
title_short Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
title_sort selinexor s immunomodulatory impact in advancing multiple myeloma treatment
topic Selinexor
XPOVIO
XPO1
Exportin-1
nuclear export
multiple myeloma
url https://www.mdpi.com/2073-4409/14/6/430
work_keys_str_mv AT kereshmehtasbihi selinexorsimmunomodulatoryimpactinadvancingmultiplemyelomatreatment
AT heikobruns selinexorsimmunomodulatoryimpactinadvancingmultiplemyelomatreatment