ArticleCancer research2024
XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 23 citations in OpenAlex.
- XPO1: From basic research to clinical treatment (Review).Oncology reports · 2026Review
- CD73 inhibitor enhances the antitumor activity of selinexor in multiple myeloma by restoring the activation of CD8Cancer gene therapy · 2026Article
- ADT and activation of HGF and WNT axes in double-null prostate cancer.Nature reviews. Urology · 2026Review
- Escorting mRNAs - the multifunctional and divergent roles of cap-chaperones in post-transcriptional gene expression.Journal of cell science · 2026Review
- Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.Clinical and translational medicine · 2026Review
- [Advances in ribosome biogenesis and targeted therapies for diffuse large B-cell lymphomas].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Review
- Integrated genomics with refined cell-of-origin subtyping distinguishes subtype-specific mechanisms of treatment resistance and relapse in diffuse large B-cell lymphoma.Blood cancer journal · 2025Article
- Targeting the undruggable MYC in cancer: the rationale of using XPO1 inhibitors.Molecular biology reports · 2025Review
- Review
- Article
- Article
- RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic-nuclear shuttling in human triple-negative breast cancer.Clinical and translational medicine · 2025Article
- Modulation of anti-tumour immunity by XPO1 inhibitors.Exploration of targeted anti-tumor therapy · 2025Review
- Multiomics Analysis of Exportin Family Reveals XPO1 as a Novel Target for Clear Cell Renal Cell Carcinoma.International journal of genomics · 2025Article
- Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer.Cell reports. Medicine · 2024Article
- A review and perspective paper: Ras oncogene gets modest, from kingpin to mere henchman.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.Nature communications · 2024Article
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Exportin-1 (XPO1), the main soluble nuclear export receptor in eukaryotic cells, is frequently overexpressed in diffuse large B-cell lymphoma (DLBCL). A selective XPO1 inhibitor, selinexor, received approval as single agent for relapsed or refractory (R/R) DLBCL. Elucidating the mechanisms by which XPO1 overexpression supports cancer cells could facilitate further clinical development of XPO1 inhibitors. We uncovered here that XPO1 overexpression increases tolerance to genotoxic stress, leading to a poor response to chemoimmunotherapy. Upon DNA damage induced by MYC expression or exogenous compounds, XPO1 bound and exported EIF4E and THOC4 carrying DNA damage repair mRNAs, thereby increasing synthesis of DNA damage repair proteins under conditions of increased turnover. Consequently, XPO1 inhibition decreased the capacity of lymphoma cells to repair DNA damage and ultimately resulted in increased cytotoxicity. In a phase I clinical trial conducted in R/R DLBCL, the combination of selinexor with second-line chemoimmunotherapy was tolerated with early indication of efficacy. Overall, this study reveals that XPO1 overexpression plays a critical role in the increased tolerance of cancer cells to DNA damage while providing new insights to optimize the clinical development of XPO1 inhibitors. SIGNIFICANCE: XPO1 regulates the dynamic ribonucleoprotein nuclear export in response to genotoxic stress to support tolerance and can be targeted to enhance the sensitivity of cancer cells to endogenous and exogenous DNA damage. See related commentary by Knittel and Reinhardt, p. 3.
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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.