ArticleThe Journal of clinical investigation2022
Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 52 citations in OpenAlex.
- Genomic Profiling of Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer after Progression on First-line Osimertinib: Phase II ORCHARD Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).Cell reports. Medicine · 2024Trial
- Multifocal ground-glass opacities in lung cancer: a narrative review of genomic evolution, immune ecology, and biology-informed clinical management.Journal of thoracic disease · 2026Review
- Ribonucleotide Reductase Inhibition Triggers Ferroptosis in Genetically Defined Subsets of Non-Small Cell Lung Cancer.Cancer research communications · 2026Article
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Durvalumab Plus Chemotherapy in Patients WithJTO clinical and research reports · 2026Article
- USP7 Stabilizes MESP1 To Promote the Malignant Progression of Non-Small Cell Lung Cancer.Applied biochemistry and biotechnology · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Fatal Disease Progression Driven by Acquired MET Amplification After EGFR-TKI Therapy in EGFR- and RBM10-Mutant Lung Adenocarcinoma.Cancer management and research · 2026Article
- Evidence for the transformation of a subset of pulmonary carcinoids to small cell lung carcinomas through shared molecular alterations.Frontiers in oncology · 2026Article
- Liquid Biopsy and Automated Next-Generation Sequencing: Achieving Results in 27 Hours Within a Community Setting.Diagnostics (Basel, Switzerland) · 2025Article
- Evaluation of gefitinib alone or combined with bevacizumab in patients withTranslational lung cancer research · 2025Article
- Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures.Cancer cell · 2025Article
- Splicing Shift of RAC1 Accelerates Tumorigenesis and Defines a Potent Therapeutic Target in Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Immunoregulatory role of pulmonary microbiota in lung cancer: a bibliometric analysis.Discover oncology · 2025Article
- Review
- RBM10 deficiency promotes brain metastasis by modulating sphingolipid metabolism in a BBB model of EGFR mutant lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- RBM10 inhibits pancreatic cancer development by suppressing immune escape through PD-1 expression.Journal of Cancer · 2025Article
- Combination of Vismodegib and Paclitaxel Enhances Cytotoxicity via Bak-mediated Mitochondrial Damage in EGFR-Mutant Non-Small Cell Lung Cancer Cells.Cell biochemistry and biophysics · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 9 institutions in 5 countries.
Funding
Abstract
Molecularly targeted cancer therapy has improved outcomes for patients with cancer with targetable oncoproteins, such as mutant EGFR in lung cancer. Yet, the long-term survival of these patients remains limited, because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations of EGFR often harbor additional co-occurring genetic alterations. This hypothesis remains untested for most genetic alterations that co-occur with mutant EGFR. Here, we report the functional impact of inactivating genetic alterations of the mRNA splicing factor RNA-binding motif 10 (RBM10) that co-occur with mutant EGFR. RBM10 deficiency decreased EGFR inhibitor efficacy in patient-derived EGFR-mutant tumor models. RBM10 modulated mRNA alternative splicing of the mitochondrial apoptotic regulator Bcl-x to regulate tumor cell apoptosis during treatment. Genetic inactivation of RBM10 diminished EGFR inhibitor-mediated apoptosis by decreasing the ratio of (proapoptotic) Bcl-xS to (antiapoptotic) Bcl-xL isoforms of Bcl-x. RBM10 deficiency was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Coinhibition of Bcl-xL and mutant EGFR overcame the resistance induced by RBM10 deficiency. This study sheds light on the role of co-occurring genetic alterations and on the effect of splicing factor deficiency on the modulation of sensitivity to targeted kinase inhibitor cancer therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.