ArticleJournal of Cancer2013
CRM1 Inhibition Sensitizes Drug Resistant Human Myeloma Cells to Topoisomerase II and Proteasome Inhibitors both In Vitro and Ex Vivo.
Article in Journal of Cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
- Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.British journal of cancer · 2022Trial
- Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors.Journal of hematology & oncology · 2016Trial
- Combination effect of Exportin 1 inhibitor (KPT-335) with doxorubicin or vincristine in canine lymphoma cell lines.The Journal of veterinary medical science · 2026Article
- Lipin1-dependent transcriptional inactivation of SREBPs contributes to selinexor sensitivity in multiple myeloma.Acta pharmacologica Sinica · 2025Article
- Review
- Selinexor in acute myeloid leukemia: therapeutic applications and current challenges.Frontiers in pharmacology · 2025Review
- Unraveling the complexity of drug resistance mechanisms to SINE, T cell-engaging therapies and CELMoDs in multiple myeloma: a comprehensive review.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance.Cell reports · 2022Article
- The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma.Translational oncology · 2022Review
- Article
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- The nuclear export protein XPO1 - from biology to targeted therapy.Nature reviews. Clinical oncology · 2021Review
- Inhibition of Kpnβ1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer.BMC cancer · 2021Article
- Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma.EJHaem · 2021Article
- Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials.Frontiers in pharmacology · 2021Review
- Targeting Nuclear Export Proteins in Multiple Myeloma Therapy.Targeted oncology · 2020Review
- Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma.Cancer research · 2020Article
- Review
- Targeted CRM1-inhibition perturbs leukemogenic NUP214 fusion proteins and exerts anti-cancer effects in leukemia cell lines withOncotarget · 2020Article
- NRG1/ERBB3 Pathway Activation Induces Acquired Resistance to XPO1 Inhibitors.Molecular cancer therapeutics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple myeloma (MM) remains an incurable disease despite improved treatments, including lenalidomide/pomalidomide and bortezomib/carfilzomib based therapies and high-dose chemotherapy with autologous stem cell rescue. New drug targets are needed to further improve treatment outcomes. Nuclear export of macromolecules is misregulated in many cancers, including in hematological malignancies such as MM. CRM1 (chromosome maintenance protein-1) is a ubiquitous protein that exports large proteins (>40 kDa) from the nucleus to the cytoplasm. We found that small-molecule Selective Inhibitors of Nuclear Export (SINE) prevent CRM1-mediated export of p53 and topoisomerase IIα (topo IIα). SINE's CRM1-inhibiting activity was verified by nuclear-cytoplasmic fractionation and immunocytochemical staining of the CRM1 cargoes p53 and topo IIα in MM cells. We found that SINE molecules reduced cell viability and induced apoptosis when used as both single agents in the sub-micromolar range and when combined with doxorubicin, bortezomib, or carfilzomib but not lenalidomide, melphalan, or dexamethasone. In addition, CRM1 inhibition sensitized MM cell lines and patient myeloma cells to doxorubicin, bortezomib, and carfilzomib but did not affect peripheral blood mononuclear or non-myeloma bone marrow mononuclear cells as shown by cell viability and apoptosis assay. Drug resistance induced by co-culture of myeloma cells with bone marrow stroma cells was circumvented by the addition of SINE molecules. These results support the continued development of SINE for patients with MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.