ArticleCancer research2026
Transfer of Damaged Mitochondria from Cancer Cells to Cancer-Associated Fibroblasts Promotes Tyrosine Kinase Inhibitor Tolerance in EGFR-Mutant Lung Cancer.
Article in Cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- Cancer-associated mitochondrial homeostasis disrupted and retrograde signaling activated.Medical oncology (Northwood, London, England) · 2026Review
- Mitochondria-Targeted Nanotherapeutics: A Promising Strategy in Modulating Mitochondrial Function, Transfer, and Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Integrated pan-cancer analysis reveals a cancer-associated fibroblast oxidative stress response signature predicting immunotherapy response and prognosis.Apoptosis : an international journal on programmed cell death · 2026Article
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Biomarker exploration for immunotherapy plus chemotherapy following resistance to third-generation EGFR-TKIs in lung adenocarcinoma.BMC cancer · 2026Article
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- Mitochondrial niches of residual disease in EGFR-mutant NSCLC: immune-constrained persistence and therapeutic interception.Frontiers in immunology · 2026Review
- The role of mitochondrial energy metabolism in drug resistance and prognosis of lung adenocarcinoma: a multi-omics and machine learning strategy for predictive and personalized therapy.Frontiers in medicine · 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Drug-tolerant persister (DTP) cells drive therapeutic resistance in EGFR-mutant lung adenocarcinoma. Using single-cell RNA sequencing, we identified a clinically significant RGS5+MYL9+ cancer-associated fibroblast (CAF) population that was associated with EGFR tyrosine kinase inhibitor (TKI) resistance and poor prognosis. These CAFs were recruited to DTP niches via CCL11 signaling, and they formed tunneling nanotubes through Miro1/RhoA activation induced by TKI-generated mitochondrial reactive oxygen species. Remarkably, RGS5+MYL9+ CAFs functioned as "metabolic sinks" by accepting tumor-derived damaged mitochondria, thereby promoting DTP survival. Treatment with fasudil, a Rho kinase inhibitor, effectively blocked mitochondrial transfer and restored sensitivity to the EGFR-TKI osimertinib in vivo. Together, this work reveals targetable stromal-tumor cross-talk that sustains DTP populations, proposing a combination therapy for overcoming EGFR-TKI resistance. SIGNIFICANCE: Pharmacological blockade of nanotube-mediated mitochondrial transfer between tumor cells and RGS5+MYL9+ fibroblasts effectively overcome tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer, offering a clinically applicable strategy to enhance EGFR inhibitor efficacy.
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.