ArticleRadiation oncology (London, England)2015
Mutant KRAS associated malic enzyme 1 expression is a predictive marker for radiation therapy response in non-small cell lung cancer.
Article in Radiation oncology (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Malic enzyme 1 contributes to tumorigenesis and lenvatinib resistance in hepatocellular carcinoma via FSP1-dependent ferroptosis evasion.Cell death & disease · 2026Article
- Deciphering enemy tactics - the narrow path to an optimal anti-cancer strategy targeting the Warburg effect.Pharmacological reports : PR · 2025Review
- WTAP contributes to platinum resistance in high-grade serous ovarian cancer by up-regulating malic acid: insights from liquid chromatography and mass spectrometry analysis.Cancer & metabolism · 2025Article
- Significance of Malic Enzyme 1 in Cancer: A Review.Current issues in molecular biology · 2025Review
- Malic enzymes in cancer: Regulatory mechanisms, functions, and therapeutic implications.Redox biology · 2024Review
- Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution.Nature communications · 2023Article
- Cellular redox homeostasis maintained by malic enzyme 2 is essential for MYC-driven T cell lymphomagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role and therapeutic targeting of glutamine metabolism in non‑small cell lung cancer (Review).Oncology letters · 2023Review
- HighCancers · 2022Article
- Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Comparative proteomic analysis of exhaled breath condensate between lung adenocarcinoma and CT-detected benign pulmonary nodule patients.Cancer biomarkers : section A of Disease markers · 2022Article
- Extracellular citrate and metabolic adaptations of cancer cells.Cancer metastasis reviews · 2021Review
- Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.Cancer medicine · 2021Article
- Role of NRF2 in Lung Cancer.Cells · 2021Review
- Review
- Therapeutic Potential of Glutamine Pathway in Lung Cancer.Frontiers in oncology · 2021Review
- Identification and Prognostic Value Exploration of Radiotherapy Sensitivity-Associated Genes in Non-Small-Cell Lung Cancer.BioMed research international · 2021Article
- Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism.Journal of molecular endocrinology · 2020Review
- Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models.International journal of molecular sciences · 2020Article
- NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2020Review
Corrections and comments
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1 author at 1 institution in 1 country.
Funding
Abstract
backgroundAdvanced non-small cell lung cancer (NSCLC) is an aggressive tumor that is treated with a combination of chemotherapy and radiation if the patient is not a candidate for surgery. Predictive biomarkers for response to radiotherapy are lacking in this patient population, making it a non-tailored therapy regimen with unknown outcome. Twenty to 30 % of NSCLC harbor an activating mutation in KRAS that may confer radioresistance. We hypothesized that mutant KRAS can regulate glutamine metabolism genes in NSCLC and maintain tumor redox balance through transamination reactions that generate cytosolic NADPH via malic enzyme 1 (ME1), which may contribute to radioresistance.
findingsA doxycycline-inducible mouse model of KRAS (G12D) driven NSCLC and patient data was analyzed from multiple publicly accessible databases including TCGA, CCLE, NCBI GEO and Project Achilles. ME1 expression was found to be mutant KRAS associated in both a NSCLC mouse model and human NSCLC cancer cell lines. Perturbing glutamine metabolism sensitized mutant KRAS, but not wild-type KRAS NSCLC cell lines to radiation treatment. NSCLC survival analysis revealed that patients with elevated ME1 and GOT1 expression had significantly worse outcomes after radiotherapy, but this was not seen after chemotherapy alone.
conclusionsKRAS driven glutamine metabolism genes, specifically ME1 and GOT1 reactions, may be a predictive marker and potential therapeutic target for radiotherapy in NSCLC.
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