ArticleBMC cancer2015
KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin [corrected] in prostate cancer models.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- A Phase II Trial of Selinexor (KPT-330) for Metastatic Triple-Negative Breast Cancer.The oncologist · 2019Trial
- Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma.BMC veterinary research · 2018Trial
- A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone- and/or Enzalutamide-Refractory Metastatic Castration-Resistant Prostate Cancer.The oncologist · 2018Trial
- Targeting Exportin-1 in Cancer: From Nuclear Export to Oncogenic Transcriptional Hubs.JMA journal · 2026Review
- On-resin Heck coupling enables small-molecule ligand discovery with covalent peptide-encoded libraries.Chemical science · 2026Article
- Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study.Blood advances · 2026Article
- Co-Targeting Nuclear Export and Translation Initiation Uncovers a Therapeutic Vulnerability in Lethal Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- SINE compounds activate exportin 1 degradation through an allosteric mechanism.Nature chemical biology · 2025Article
- Targeting CRM1 for Progeria Syndrome Therapy.Aging cell · 2025Article
- XPO1 serves as a prognostic marker involving AKT/MAPK/TGFBR1 pathway in OSCC.Cancer medicine · 2024Article
- A novel application of XPO1 inhibition for the treatment of myelofibrosis.Blood neoplasia · 2024Review
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin.Communications biology · 2024Article
- Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation.Nature communications · 2024Article
- Treatment of multiple myeloma with selinexor: a review.Therapeutic advances in hematology · 2024Review
- Selinexor for the treatment of recurrent or metastatic salivary gland tumors: Results from the GEMS-001 clinical trial.Cancer medicine · 2023Article
- The Complex Relationship between Hypoxia Signaling, Mitochondrial Dysfunction and Inflammation in Calcific Aortic Valve Disease: Insights from the Molecular Mechanisms to Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Synthetic lethal targeting of TET2-mutant haematopoietic stem and progenitor cells by XPO1 inhibitors.British journal of haematology · 2023Article
- The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: a comprehensive review.Journal of cancer research and clinical oncology · 2023Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsIncreased expression of Chromosome Region Maintenance (CRM-1)/exportin-1 (XPO-1) has been correlated with poor prognosis in several aggressive tumors, making it an interesting therapeutic target. Selective Inhibitor of Nuclear Export (SINE) compounds bind to XPO-1 and block its ability to export cargo proteins. Here, we investigated the effects of a new class of SINE compounds in models of prostate cancer. MATERIAL AND
methodsWe evaluated the expression of XPO-1 in human prostate cancer tissues and cell lines. Next, six SINE (KPT-127, KPT-185, KPT-205, KPT-225, KPT-251 and KPT-330) compounds having different potency with broad-spectrum, tumor-selective cytotoxicity, tolerability and pharmacokinetic profiles were tested in a panel of prostate cancer cells representing distinct differentiation/progression states of disease and genotypes. Two SINE candidates for clinical trials (KPT-251 and KPT-330) were also tested in vivo in three cell models of aggressive prostate cancer engrafted in male nude mice. RESULTS AND
conclusionsXPO-1 is overexpressed in prostate cancer compared to normal or hyperplastic tissues. Increased XPO-1 expression, mainly in the nuclear compartment, was associated with increased Gleason score and bone metastatic potential supporting the use of SINEs in advanced prostate cancer. SINE compounds inhibited proliferation and promoted apoptosis of tumor cells, but did not affect immortalized non-transformed prostate epithelial cells. Nuclei from SINE treated cells showed increased protein localization of XPO-1, survivin and cyclin D1 followed by degradation of these proteins leading to cell cycle arrest and apoptosis. Oral administration of KPT-251 and KPT-330 in PC3, DU145 and 22rv1 tumor-bearing nude mice reduced tumor cell proliferation, angiogenesis and induced apoptosis. Our results provide supportive evidence for the therapeutic use of SINE compounds in advanced/castration resistant prostate cancers and warrants further clinical investigation.
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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.