Trial reportJournal of hematology & oncology2016
Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors.
Trial report in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02186834 (Investigator-Initiated Phase I/II Clinical Trial of Selinexor), which is not on this map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Investigator-Initiated Phase I/II Clinical Trial of Selinexor (KPT-330) and Liposomal Doxorubicin for Relapsed and Refractory Multiple Myeloma
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk.American journal of hematology · 2021Trial
- Trial
- Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.Nature communications · 2026Article
- Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape.ESMO open · 2026Review
- Efficacy of an XPO1 inhibitor in combination with irinotecan in a preclinical colorectal cancer model.Frontiers in oncology · 2026Article
- Exportin 1 inhibitor KPT‑330 reverses oxaliplatin resistance via p53 nuclear retention in colorectal cancer.International journal of molecular medicine · 2026Article
- XPO1 inhibitor selinexor enhances the apoptotic effect of azacitidine in T-cell lymphoma with TET2/RHOA mutations via JAK3/STAT3 axis.Cell communication and signaling : CCS · 2025Article
- Cracking melanoma's armor: Supramolecular dual-strike on XPO1 and β-catenin to overcome resistance.Journal of advanced research · 2025Article
- XPO1/Exportin-1 in Acute Myelogenous Leukemia; Biology and Therapeutic Targeting.Biomolecules · 2025Review
- Targeting deubiquitinase USP7-mediated stabilization of XPO1 contributes to the anti-myeloma effects of selinexor.Journal of translational medicine · 2025Article
- Multiple myeloma inhibitory effects of natural compounds: enhancement through nanoparticle carriers.Frontiers in pharmacology · 2025Review
- The impact of high-risk cytogenetic abnormalities in extramedullary multiple myeloma in the era of novel agents: insights from a multicenter study.BMC cancer · 2024Article
- Selinexor combined with bortezomib, lenalidomide, and dexamethasone for the treatment of newly diagnosed multiple myeloma with extramedullary disease.Scientific reports · 2024Observational
- In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells.Scientific reports · 2024Article
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- Treatment of multiple myeloma with selinexor: a review.Therapeutic advances in hematology · 2024Review
- CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma.Cancer research · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAcquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease.
methodsWe investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. Mechanistic studies were performed to assess co-localization of topoisomerase II alpha (TOP2A), DNA damage, and siRNA knockdown of drug targets.
resultsSelinexor was found to restore sensitivity of multidrug-resistant 8226B25, 8226Dox6, 8226Dox40, and U266PSR human MM cells to doxorubicin to levels found in parental myeloma cell lines. NOD/SCID-γ mice challenged with drug-resistant or parental U266 human MM and treated with selinexor/PLD had significantly decreased tumor growth and increased survival with minimal toxicity. Selinexor/doxorubicin treatment selectively induced apoptosis in CD138/light-chain-positive MM cells without affecting non-myeloma cells in ex vivo-treated bone marrow aspirates from newly diagnosed or relapsed/refractory MM patients. Selinexor inhibited XPO1-TOP2A protein complexes (proximity ligation assay), preventing nuclear export of TOP2A in both parental and multidrug-resistant MM cell lines. Selinexor/doxorubicin treatment significantly increased DNA damage (comet assay/γ-H2AX) in both parental and drug-resistant MM cells. TOP2A knockdown reversed both the anti-tumor effect and significantly reduced DNA damage induced by selinexor/doxorubicin treatment.
conclusionsThe combination of an XPO1 inhibitor and liposomal doxorubicin was highly effective against acquired drug resistance in in vitro MM models, in in vivo xenograft studies, and in ex vivo samples obtained from patients with relapsed/refractory myeloma. This drug combination synergistically induced TOP2A-mediated DNA damage and subsequent apoptosis. In addition, based on our preclinical data, we have initiated a phase I/II study with the XPO1 inhibitor selinexor and PLD (ClinicalTrials.gov NCT02186834). Initial results from both preclinical and clinical trials have shown significant promise for this drug combination for the treatment of 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.