ArticleScience (New York, N.Y.)2015
Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 510 papers, 3 of them syntheses that pooled it.
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.
A Randomized Phase Ⅲ Study of IV Ascorbic Acid in Combination With FOLFOX+/- Bevacizumab vs Treatment With FOLFOX+/- Bevacizumab Alone as First-line Therapy for Advanced Colorectal Cancer
Intravenous Ascorbate Plus Gemcitabine/Carboplatin: A Novel and Cost-Effective Alternative With Evident Efficacy in Patients With Muscle Invasive Bladder Cancer
Who cites it
510 citing papers in PubMed, 3 syntheses or guidelines pooled it, 900 citations in OpenAlex.
- The mechanisms and drug therapies of colorectal cancer and epigenetics: bibliometrics and visualized analysis.Frontiers in pharmacology · 2024Pooled it
- Machine learning-based meta-analysis of colorectal cancer and inflammatory bowel disease.PloS one · 2023Pooled it
- Circulating vitamin C and digestive system cancers: Mendelian randomization study.Clinical nutrition (Edinburgh, Scotland) · 2022Pooled it
- A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study).Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Combined Molecular Hydrogen and Vitamin C Treatment in Irradiated Normal and Cancer Cell Models: An Exploratory In Vitro Study and Case Reports.Medical sciences (Basel, Switzerland) · 2026Article
- Exploiting vitamin C as a prooxidant to activate ROS-responsive prodrugs for potent and selective tumor killing.Redox biology · 2026Article
- Fractionated high-dose vitamin c sustains higher plasma trough concentrations in advanced solid tumors: a phase I clinical study.Translational oncology · 2026Article
- Beyond redox: vitamin C in signaling, epigenetic regulation and protein modification-relevance to cancer therapy.Clinical epigenetics · 2026Review
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- Review
- The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.Antioxidants (Basel, Switzerland) · 2026Review
- PARP inhibition and pharmacological ascorbate demonstrate synergy in castration-resistant prostate cancer.Molecular oncology · 2026Article
- Conserved principles of central carbon partitioning in Hippo-Yorkie-drivenbioRxiv : the preprint server for biology · 2026Article
- Activated astrocytes increase dehydroascorbic acid uptake, changing intracellular metabolism and vitamin C recycling and emulating neuropathological conditions.Redox biology · 2026Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Clostridium dalinum: A Novel Lactic Acid Bacterium with Excellent Antioxidant and Anti-inflammatory Functions Through NF-κB, Keap1-Nrf2-ARE Signaling Pathways.Probiotics and antimicrobial proteins · 2026Article
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- Review
- Threonic acid, an ascorbic acid metabolite, synergizes with intermittent fasting to ameliorate obesity.Experimental & molecular medicine · 2026Article
- Mitochondrial Redox Vulnerabilities in Triple-Negative Breast Cancer: Integrative Perspectives and Emerging Therapeutic Strategies.Metabolites · 2026Review
450 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.
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.