ArticleOncotarget2016
Heterozygous mutation of cysteine528 in XPO1 is sufficient for resistance to selective inhibitors of nuclear export.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- 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
- Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Preclinical characterization of a reversible XPO1 inhibitor for cancer therapy.Nature communications · 2026Article
- Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.Clinical and translational medicine · 2026Review
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Review
- Cysteine Alkylation in Enzymes and Transcription Factors: A Therapeutic Strategy for Cancer.Cancers · 2025Review
- 4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.PloS one · 2025Article
- Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation.Nature chemical biology · 2024Article
- C646 degrades Exportin-1 to modulate p300 chromatin occupancy and function.Cell chemical biology · 2024Article
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.Nature communications · 2024Article
- 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
- Treatment of multiple myeloma with selinexor: a review.Therapeutic advances in hematology · 2024Review
- Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.Human genomics · 2022Article
- A Three-Gene Signature Predicts Response to Selinexor in Multiple Myeloma.JCO precision oncology · 2022Article
- Therapeutic Targeting of Exportin-1 in Childhood Cancer.Cancers · 2021Review
- Next-Generation Sequencing for Clinical Management of Multiple Myeloma: Ready for Prime Time?Frontiers in oncology · 2020Review
- The past, present, and future of CRM1/XPO1 inhibitors.Stem cell investigation · 2019Review
- Nuclear Export Inhibition for Pancreatic Cancer Therapy.Cancers · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exportin-1 (CRM1/XPO1) is a crucial nuclear export protein that transports a wide variety of proteins from the nucleus to the cytoplasm. These cargo proteins include tumor suppressors and growth-regulatory factors and as such XPO1 is considered a potential anti-cancer target. From this perspective, inhibition of the XPO1-mediated nuclear export by selective inhibitor of nuclear export (SINE) compounds has shown broad-spectrum anti-cancer activity. Furthermore, the clinical candidate SINE, selinexor, is currently in multiple phase I/II/IIb trials for treatment of cancer. Resistance against selinexor has not yet been observed in the clinic, but in vitro selection of resistance did not reveal any mutations in the target protein, XPO1. However, introduction of a homozygous mutation at the drug's target site, the cysteine 528 residue inside the XPO1 cargo-binding pocket, by genetic engineering, confers resistance to selinexor. Here we investigated whether this resistance to selinexor is recessive or dominant. For this purpose we have engineered multiple leukemia cell lines containing heterozygous or homozygous C528S substitutions using CRISPR/Cas9-mediated genome editing. Our findings show that heterozygous mutation confers similar resistance against selinexor as homozygous substitution, demonstrating that SINE resistance can be obtained by a single and dominant mutation of the cysteine528 residue in XPO1.
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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.