ReviewOncogene2021
Therapeutic targeting of the mitochondrial one-carbon pathway: perspectives, pitfalls, and potential.
Review in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 61 citations in OpenAlex.
- 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
- Skeletal muscle mitochondrial-methylation-neurotransmitter crosstalk: a novel synergistic model of betaine, tyrosine, and Cordyceps for exercise performance in older adults, individuals with metabolic disorders, and healthy populations.Frontiers in nutrition · 2026Review
- Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.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
- Redox-Regulated Pathways in Glioblastoma Stem-like Cells: Mechanistic Insights and Therapeutic Implications.Brain sciences · 2025Review
- Inhibition of Purine Metabolism Promotes the Differentiation of Neuroblastoma Driven by MYCN.Cancer medicine · 2025Article
- Understanding microRNA-Mediated Chemoresistance in Colorectal Cancer Treatment.International journal of molecular sciences · 2025Review
- ALDH1L2 drives HCC progression through TAM polarization.JHEP reports : innovation in hepatology · 2025Article
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- 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
- G2 arrest primes hematopoietic stem cells for megakaryopoiesis.Cell reports · 2024Article
- Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.Nature communications · 2024Article
- MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions.npj metabolic health and disease · 2024Review
- Structural Characterization of 5-Substituted Pyrrolo[3,2-Biochemistry · 2024Article
- SHMT2 promotes papillary thyroid cancer metastasis through epigenetic activation of AKT signaling.Cell death & disease · 2024Article
- Identification of Hypoxia and Mitochondrial-related Gene Signature and Prediction of Prognostic Model in Lung Adenocarcinoma.Journal of Cancer · 2024Article
- Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024Review
- Targeting SHMTs and MTHFDs in cancer: attractive opportunity for anti-tumor strategy.Frontiers in pharmacology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most of the drugs currently prescribed for cancer treatment are riddled with substantial side effects. In order to develop more effective and specific strategies to treat cancer, it is of importance to understand the biology of drug targets, particularly the newly emerging ones. A comprehensive evaluation of these targets will benefit drug development with increased likelihood for success in clinical trials. The folate-mediated one-carbon (1C) metabolism pathway has drawn renewed attention as it is often hyperactivated in cancer and inhibition of this pathway displays promise in developing anticancer treatment with fewer side effects. Here, we systematically review individual enzymes in the 1C pathway and their compartmentalization to mitochondria and cytosol. Based on these insight, we conclude that (1) except the known 1C targets (DHFR, GART, and TYMS), MTHFD2 emerges as good drug target, especially for treating hematopoietic cancers such as CLL, AML, and T-cell lymphoma; (2) SHMT2 and MTHFD1L are potential drug targets; and (3) MTHFD2L and ALDH1L2 should not be considered as drug targets. We highlight MTHFD2 as an excellent therapeutic target and SHMT2 as a complementary target based on structural/biochemical considerations and up-to-date inhibitor development, which underscores the perspectives of their therapeutic potential.
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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.