Evidence map›Paper›PMID 40834985›Full record

ArticleCancer letters2025

Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in anaplastic thyroid cancer through enhanced activation of oxidative stress that leads to apoptosis.

Chandrayee Ghosh, Tejinder Pal Khaket, Viswanath Gunda, Zhongyue Yang, Jiangnan Hu, Eden Demissie Alamaw, Lisa Zhang, Ya-Qin Zhang, Min Shen, Yasmine Tabdili and 3 more

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In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Chandrayee GhoshDepartment of Surgery, Stanford University, Stanford, CA, USA. Electronic address: cghosh@stanford.edu.
Tejinder Pal KhaketDepartment of Surgery, Stanford University, Stanford, CA, USA.
Viswanath GundaDepartment of Surgery, Stanford University, Stanford, CA, USA.
Zhongyue YangDepartment of Surgery, Stanford University, Stanford, CA, USA.
Jiangnan HuDepartment of Surgery, Stanford University, Stanford, CA, USA.
Eden Demissie AlamawDepartment of Comparative Medicine, Veterinary Service Center, Stanford University, Stanford, CA, USA.
Lisa ZhangEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Ya-Qin ZhangNational Center for Advancing Translational Sciences, National Institute of Health, Bethesda, MD, USA.
Min ShenNational Center for Advancing Translational Sciences, National Institute of Health, Bethesda, MD, USA.
Yasmine TabdiliUniversity of Arizona, College of Medicine, Tucson, AZ, USA.
Myriem BoufraqechSurgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Rodas KassuDepartment of Surgery, Stanford University, Stanford, CA, USA.
Electron KebebewDepartment of Surgery, Stanford University, Stanford, CA, USA. Electronic address: kebebew@stanford.edu.

Funding

Therapeutic targets and novel anticancer agents for endocrine cancersZIABC011286 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NILUBOL, NARIS · 2010 to 2025
$16.6M
Intramural NIH HHS ZIA BC011286
6 · The paper itself

Abstract

Anaplastic thyroid cancer (ATC) has one of the highest mortality rates of all human malignancies and has no cure. We used combination drug matrix screening of highly active compounds and identified that combination of nitazoxanide and auranofin was one of those with the highest synergistic anticancer activity. We investigated its synergistic anticancer activity and mechanism of action in preclinical ATC models. We performed in vitro, ex vivo, and in vivo ATC models to evaluate the synergistic anticancer activity and the mechanism of action of this combination. Combination nitazoxanide and auranofin treatment synergistically inhibited cellular proliferation, colony formation, and cellular migration compared to control and single agents. Combination treatment also significantly reduced ATC cell line and patient-derived ATC spheroid size. Nitazoxanide alone and in combination with auranofin caused ER stress and apoptosis. Auranofin alone and in combination with nitazoxanide induced activation of the ROS generating pathway. This led to enhanced increase in ROS and MDA levels with combination treatment associated with upregulation of HMOX-1 and cell death that was reversed by N-acetyl cysteine (NAC). The combination significantly inhibited tumor growth in vivo in 8505C ATC cells, and C643 ATC cells, without significant treatment-related toxicity. Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in vitro, ex vivo, and in vivo in ATC, which is due to enhanced oxidative stress and induction of apoptosis compared to single-drug treatment. Both drugs are FDA approved; their combination is a potential candidate for evaluation in a clinical trial for ATC therapy.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsApoptosisAuranofinOxidative StressThiazolesThyroid Carcinoma, AnaplasticThyroid NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationDrug SynergismFemaleHumansMiceMice, NudeAuranofinnitazoxanideNitro CompoundsReactive Oxygen SpeciesThiazolesAnaplastic thyroid cancerAuranofinCell deathCombination therapyNitazoxanideSynergism

Identifiers

PMID40834985
PMCPMC12670439

What OpenQuestion holds

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Registered trials

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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.