ArticleCancers2024
GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.
Article in Cancers, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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
10 citing papers in PubMed.
- Neural regulation of cancer: from synaptic integration to neuro-immune regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.Biology · 2026Review
- Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.Frontiers in oncology · 2026Review
- Progression and Metastasis of Lung Cancer: Clinical Features, Molecular Mechanisms, and Clinical Managements.MedComm · 2025Review
- GABA regulates metabolic reprogramming to mediate the development of brain metastasis in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Integrated multi-omics reveals GABARAP-mediated mitophagy and pyruvate metabolism as key drivers of osteosarcoma progression.Frontiers in immunology · 2025Article
- Mitophagy in the mechanisms of treatment resistance in solid tumors.Oncology reviews · 2025Review
- The double role of GABAergic system in systemic tumors: an updated review.Frontiers in oncology · 2025Review
- Review
- Consortium for Intracranial Metastasis Academic Research (CIMARa): Global interdisciplinary collaborations to improve outcomes of patient with brain metastases.Neuro-oncology advancesReview
Corrections and comments
- Update of
Authors and funding
22 authors.
Funding
Abstract
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity.
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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.