ArticleJournal of the National Cancer Institute2019
Modulation of Redox Homeostasis by Inhibition of MTHFD2 in Colorectal Cancer: Mechanisms and Therapeutic Implications.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 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
118 citing papers in PubMed, 185 citations in OpenAlex.
- A five-gene TAM and MYCN signature predicts prognosis and identifies MTHFD2 as a therapeutic target in neuroblastoma.Discover oncology · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Investigating the oncogenic potential of MTHFD2 in oral squamous cell carcinoma.Journal of cancer research and clinical oncology · 2026Article
- Hypoxia facilitates triple-negative breast cancer stem cells enrichment and stemness maintenance through oxidized ataxia telangiectasia mutated-induced one-carbon metabolism.World journal of stem cells · 2026Article
- MTHFD2 is required for DNA repair and implicated in LUAD radiotherapy resistance.Journal of translational medicine · 2026Article
- Integrative transcriptomic and single-cell analysis reveals mitochondrial-related gene biomarkers in heart failure with preserved ejection fraction.Scientific reports · 2025Article
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025Review
- SIRT5-mediated desuccinylation of MTHFD2 enhances chemoresistance in breast cancer cells by reducing therapy-induced senescence.Communications biology · 2025Article
- Mitochondrial one-carbon metabolism is required for TGF-β-induced glycine synthesis and fibrotic responses.Nature communications · 2025Article
- Theranostic Potential of Copper-64 ATSM Targeting MTHFD2: An In Silico Perspective on Hypoxia-Selective Imaging and Therapy.Cell biochemistry and biophysics · 2025Article
- Article
- MTHFD2 promotes esophageal squamous cell carcinoma progression via m6A modification‑mediated upregulation and modulation of the PEBP1‑RAF1 interaction.International journal of molecular medicine · 2025Article
- Article
- Targeting MTHFD2 alters metabolic homeostasis and synergizes with bortezomib to inhibit multiple myeloma.Cell death discovery · 2025Article
- MTHFD2 marks pemetrexed resistance in pulmonary adenocarcinoma with EGFR wild type.Discover oncology · 2025Article
- Development of Potent and Selective Inhibitors of Methylenetetrahydrofolate Dehydrogenase 2 for Targeting Acute Myeloid Leukemia: SAR, Structural Insights, and Biological Characterization.Journal of medicinal chemistry · 2024Article
- MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.Redox report : communications in free radical research · 2024Article
- Nuclear localization of MTHFD2 is required for correct mitosis progression.Nature communications · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundOvercoming oxidative stress is a critical step for tumor progression; however, the underlying mechanisms in colorectal cancer (CRC) remain unclear.
methodsWe investigated nicotinamide adenine dinucleotide (phosphate) (NAD(P))-dependent enzyme methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, clinical relevance, redox modification, and molecular mechanisms using the CRC cells and tissues (n = 462 paired samples). The antitumor effects of MTHFD2 inhibitor LY345899 on CRC tumorigenesis and metastasis were evaluated in vitro and in vivo. Data analysis used Kaplan-Meier, Pearson's correlation, and Student t test where appropriate. All statistical tests were two-sided.
resultsHere, we report that the patients with high expression of MTHFD2 have a shorter overall survival (HR = 1.62, 95% CI = 1.12 to 2.36, P = .01) and disease-free survival (HR = 1.55, 95% CI = 1.07 to 2.27, P = .02) than patients with low MTHFD2 expression. Suppression of MTHFD2 disturbs NADPH and redox homeostasis and accelerates cell death under oxidative stress, such as hypoxia or anchorage independence (P ≤ .01 for all). Also, genetic or pharmacological inhibition of MTHFD2 suppresses CRC cell growth and lung and peritoneal metastasis in cell-based xenografts (n = 5-8 mice per group). Importantly, LY345899 treatment statistically significantly suppresses tumor growth and decreases the tumor weight in CRC patient-derived xenograft models (n = 10 mice per group, mean [SD] tumor weight of the vehicle-treated group was 1.83 [0.19] mg vs 0.74 [0.30] mg for the LY345899-treated group, P < .001).
conclusionsOur study presents evidence that MTHFD2 confers redox homeostasis and promotes CRC cell growth and metastasis. The folate analog LY345899 as MTHFD2 inhibitor displays therapeutic activity against CRC and warrants further clinical investigation for CRC treatment.
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.