ArticleScience translational medicine2023
Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 41 citations in OpenAlex.
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- CD73 inhibitor enhances the antitumor activity of selinexor in multiple myeloma by restoring the activation of CD8Cancer gene therapy · 2026Article
- XPO1-mediated TRIM21 nuclear export reprograms TREM2+ macrophage polarization by targeting IRF3 to augment anti-PD-1 efficacy in small cell lung cancer.Nature communications · 2026Article
- Basic Clinical Bidirectional Empowerment: Synergistic Breakthrough in Molecular Mechanisms and Clinical Management of Small Cell Cervical Carcinoma.International journal of molecular sciences · 2026Review
- Co-Targeting Nuclear Export and Translation Initiation Uncovers a Therapeutic Vulnerability in Lethal Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- CCT3-mediated regulation of XPO1/RB1 axis stability promotes cellular senescence and tumor progression in clear cell renal carcinoma.iScience · 2026Article
- Lineage plasticity: a new dilemma in lung cancer treatment.Molecular biology reports · 2026Review
- Targeting XPO1: A new perspective for malignant solid tumor especially small cell lung cancer.Chinese medical journal · 2026Article
- Review
- Immunotherapy for small cell lung cancer: current challenges and prospects.Experimental hematology & oncology · 2025Review
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures.Cancer cell · 2025Article
- Molecular mechanisms and clinical insights in transformed small cell lung cancer: a narrative review.Translational lung cancer research · 2025Review
- XPO1 as a key regulator in small cell lung cancer: mechanisms, biomarkers, and therapeutic implications.Cancer biology & medicine · 2025Article
- Nuclear to Cytoplasmic Transport Is a Druggable Dependency in HDAC7-driven Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- [Crosstalk between Tumor Cells and Neural Signals in Neuroendocrine Carcinoma Metastasis: Communication Hijacking Based Perspective].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Review
- Histologic transformation after targeted therapy resistance in driver gene-positive NSCLC: mechanisms and therapeutic challenges.Therapeutic advances in medical oncology · 2025Review
- Case report: Anlotinib plus oral etoposide: a potential salvage therapy based on insights from EGFR-TKI-resistant SCLC transformation PDX and clinical settings.Frontiers in oncology · 2025Article
- Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies.Recent patents on anti-cancer drug discovery · 2025Review
Corrections and comments
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Authors and funding
25 authors at 3 institutions in 2 countries.
Funding
Abstract
In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here, we explored the role of exportin 1 in NE transformation. We observed up-regulated exportin 1 in lung and prostate pretransformation adenocarcinomas. Exportin 1 was up-regulated after genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation in different TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the aromatase inhibitor enzalutamide and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs to standard cytotoxics. Together, these data nominate exportin 1 inhibition as a potential therapeutic target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma.
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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.