ArticleNational science review2024
Integrative study of lung cancer adeno-to-squamous transition in EGFR TKI resistance identifies RAPGEF3 as a therapeutic target.
Article in National science review, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Mutant p53 sensitizes KRAS-driven lung adenocarcinoma to immunotherapy by repressing SPP1.Science advances · 2026Article
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- HNPP: Higher-order network-based personalized PageRank for detecting critical phase in complex biological systems.PLoS computational biology · 2026Article
- Efficacy and mechanisms of immune checkpoint inhibitors in late-stage EGFR-mutated non-small cell lung cancer following targeted therapy resistance.Frontiers in immunology · 2026Review
- Squamous transformation of EGFR-mutant lung adenocarcinoma after EGFR-TKI therapy: clonal continuity, tissue-based diagnosis, and therapeutic evidence gaps.Frontiers in oncology · 2026Review
- Taxanes Versus Pemetrexed After Osimertinib Resistance in EGFR-Mutated NSCLC: A Retrospective Cohort with Two-Model In Vitro Validation.Cancer management and research · 2026Article
- Identification of RAPGEF3 as the therapeutic vulnerability of basal-subtype lung squamous cell carcinoma.Oncogene · 2025Article
- Single-Cell RNA Sequencing in Unraveling Acquired Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: New Perspectives.International journal of molecular sciences · 2025Review
- Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although adeno-to-squamous transition (AST) has been observed in association with resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in clinic, its causality, molecular mechanism and overcoming strategies remain largely unclear. We here demonstrate that squamous transition occurs concomitantly with TKI resistance in PC9-derived xenograft tumors. Perturbation of squamous transition via DNp63 overexpression or knockdown leads to significant changes in TKI responses, indicative of a direct causal link between squamous transition and TKI resistance. Integrative RNA-seq, ATAC-seq analyses and functional studies reveal that FOXA1 plays an important role in maintaining adenomatous lineage and contributes to TKI sensitivity. FOXM1 overexpression together with FOXA1 knockout fully recapitulates squamous transition and TKI resistance in both PC9 xenografts and patient-derived xenograft (PDX) models. Importantly, pharmacological inhibition of RAPGEF3 combined with EGFR TKI efficiently overcomes TKI resistance, especially in RAPGEF3
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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 Socratic graph.