Evidence map›Paper›PMID 33804775›Full record

ReviewCancers2021

High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients.

Manuela Giansanti, Terry Karimi, Isabella Faraoni, Grazia Graziani

Open access · goldAbstract readReview
In one paragraph

Review in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Tumor-Selective and Chemical Activation Strategies for Nitrogen Mustard Prodrugs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. The Involvement of Ascorbic Acid in Cancer Treatment.Molecules (Basel, Switzerland) · 2024
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Manuela GiansantiDepartment of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.ORCID 0000-0003-1948-0481
Terry KarimiDepartment of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Isabella FaraoniDepartment of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.ORCID 0000-0003-0100-6247
Grazia GrazianiDepartment of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.ORCID 0000-0002-0221-768X
University of Rome Tor Vergata · IT

Funding

Associazione Italiana per la Ricerca sul Cancro ID. 20353 project
6 · The paper itself

Abstract

High-dose vitamin C has been proposed as a potential therapeutic approach for patients with advanced tumors who failed previous treatment with chemotherapy. Due to vitamin C complex pharmacokinetics, only intravenous administration allows reaching sufficiently high plasma concentrations required for most of the antitumor effects observed in preclinical studies (>0.250 mM). Moreover, vitamin C entry into cells is tightly regulated by SVCT and GLUT transporters, and is cell type-dependent. Importantly, besides its well-recognized pro-oxidant effects, vitamin C modulates TET enzymes promoting DNA demethylation and acts as cofactor of HIF hydroxylases, whose activity is required for HIF-1α proteasomal degradation. Furthermore, at pharmacological concentrations lower than those required for its pro-oxidant activity (<1 mM), vitamin C in specific genetic contexts may alter the DNA damage response by increasing 5-hydroxymethylcytosine levels. These more recently described vitamin C mechanisms offer new treatment opportunities for tumors with specific molecular defects (e.g., HIF-1α over-expression or TET2, IDH1/2, and WT1 alterations). Moreover, vitamin C action at DNA levels may provide the rationale basis for combination therapies with PARP inhibitors and hypomethylating agents. This review outlines the pharmacokinetic and pharmacodynamic properties of vitamin C to be taken into account in designing clinical studies that evaluate its potential use as anticancer agent.

Indexed as

5-hydroxymethylcytosineascorbateDNA damagehypomethylating agentsIDH1/2PARP inhibitorsROSTET2vitamin CWT1

Identifiers

PMID33804775
PMCPMC8003833
OpenAlexW3137645085

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.