ArticleOncotarget2017
Exploiting ROS and metabolic differences to kill cisplatin resistant lung cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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.
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Who cites it
74 citing papers in PubMed, 104 citations in OpenAlex.
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Cancer Cell Dormancy and Chemotherapy Resistance.Journal of Cancer · 2026Review
- The Interdependence of Carbon Substrates and Metabolic Pathways Enables the Metabolic Plasticity of Cancer Cells.Advances in experimental medicine and biology · 2026Review
- Nutritional approaches in combating therapeutic resistance and enhancing treatment efficacy in cancer: the impact of ketogenic diets.Nutrition & metabolism · 2025Review
- Article
- Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.Fundamental & clinical pharmacology · 2025Article
- Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.Cancer medicine · 2025Review
- A Novel Approach for Cisplatin-Resistant Esophageal Squamous Cell Carcinoma via Amino Acid Transporter LAT1 Inhibition.Cancer medicine · 2025Article
- Lactate dehydrogenase A: a potential new target for tumor drug resistance intervention.Journal of translational medicine · 2025Review
- Riluzole in Combination with mFOLFOX6 and Bevacizumab in Treating Patients with Metastatic Colorectal Cancer: A Phase I Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy.Journal of personalized medicine · 2025Review
- Repurposing riluzole as an anti-osteosarcoma agent.Frontiers in oncology · 2025Article
- Highly Multiplexed Tissue Imaging in Precision Oncology and Translational Cancer Research.Cancer discovery · 2024Review
- Review
- Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect.Cancers · 2024Article
- Mitochondrion: Main organelle in orchestrating cancer escape from chemotherapy.Cancer reports (Hoboken, N.J.) · 2024Review
- NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter. Thus, blocking glutamate flux using riluzole (an amyotropic lateral sclerosis approved drug) can selectively kill CR cells in vitro and in vivo. However, we discovered here that glutathione suppression is not the primary pathway in eradicating the CR cells. Riluzole can lead to further decrease in NAD+ (nicotinamide adenine dinucleotide) and lactate dehydrogenase-A (LDHA) expressions which in turn further heightened oxidative stress in CR cells. LDHA knocked-down cells became hypersensitive to riluzole treatments and possessed increased levels of ROS. Addition of NAD+ re-stabilized LDHA and reversed riluzole induced cell death. Thus far, no drugs are available which could overcome cisplatin resistance or kill cisplatin resistant cells. CR cells possess high levels of ROS and undergo metabolic reprogramming. These metabolic adaptations can be exploited and targeted by riluzole. Riluzole may serve as a dual-targeting agent by suppression LDHA and blocking xCT antiporter. Repurposing of riluzole should be considered for future treatment of cisplatin resistant lung cancer patients.
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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.