Evidence map›Paper›PMID 42263414›Full record

ArticleRedox biology2026

Exploiting vitamin C as a prooxidant to activate ROS-responsive prodrugs for potent and selective tumor killing.

Taufeeque Ali, Thilini Nimasha Fernando Ponnamperumage, Cody Joshua Miller, Daniel Li, Wasiu Olaniyi Awoyera, Alexis Kimberly Peterson, Hanlun Gao, Jatin Pandey, Julia Anna Rose Jakusz, Heli Fan and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Tumor-Selective and Chemical Activation Strategies for Nitrogen Mustard Prodrugs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  2. HJournal of medicinal chemistry · 2025
    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

17 authors.

Taufeeque AliDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Thilini Nimasha Fernando PonnamperumageDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Cody Joshua MillerDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Daniel LiDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Wasiu Olaniyi AwoyeraDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Alexis Kimberly PetersonDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Hanlun GaoDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Jatin PandeyDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Julia Anna Rose JakuszDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Heli FanDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Gilbert Edward KoelschDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Leggy A ArnoldDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA.
Julie M JornsDepartment of Pathology, Medical College Wisconsin, Milwaukee, WI, USA.
Yee Chung ChengDepartment of Hematology and Oncology and Department of Medicine, Medical College Wisconsin, Milwaukee, WI, USA.
Avik RoyResearch and Development Laboratory, Simmaron Research Institute, Milwaukee, WI, USA.
Gang ZhouGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Xiaohua PengDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E. Kenwood Boulevard, Milwaukee, WI, 53211, USA. Electronic address: pengx@uwm.edu.

Funding

Novel DNA cross-linking agents and combination strategies for tumor-specific activationR15CA277656 · NCI · UNIVERSITY OF WISCONSIN MILWAUKEE · PI PENG, XIAOHUA · 2023 to 2023
$462k
NCI NIH HHS R15 CA277656
6 · The paper itself

Abstract

Developing targeted cancer therapy with minimal side effects remains a significant challenge. Oxidative stress-based cancer therapies have gained traction in recent years. However, challenges such as limited tumor selectivity and therapeutic durability often hinder their clinical application. Here, we report a novel strategy of combining ROS-responsive prodrugs with prooxidants to achieve potent, durable, and selective tumor killing effects. This approach leverages pro-oxidants (i.e. ascorbate) to amplify oxidative stress within tumors, sensitizing cancer cells to ROS-responsive prodrugs. Both in vitro and in vivo studies confirm the anticancer synergism and selectivity of this combination therapy, which achieved complete tumor regression without recurrence, significantly outperforming single-agent treatments. This combination therapy is effective against hard-to-treat cancers like triple-negative breast cancers. Our findings highlight the potential of targeting tumor redox mechanisms through a combination of ROS-responsive prodrugs and pro-oxidants, offering a promising avenue for repurposing these agents in cancer therapy.

Indexed as

Antineoplastic AgentsAscorbic AcidProdrugsReactive Oxygen SpeciesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorDrug SynergismFemaleHumansMiceOxidative StressXenograft Model Antitumor AssaysAntineoplastic AgentsAscorbic AcidProdrugsReactive Oxygen SpeciesCombination therapyComplete tumor regressionROS-Generating agentsROS-Responsive prodrugsSynergistic anticancer effectsTriple negative breast cancerVitamin C

Identifiers

PMID42263414
PMCPMC13273229

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.