Evidence map›Paper›PMID 41005298›Full record

ArticleCell reports. Medicine2025

Vorapaxar enhanced mitochondria-associated ferroptosis primes cancer immunotherapy via targeting FOXO1/HMOX1 axis.

Qian Zhou, Yuming Sun, Songtao Du, Yating Dian, Lei Yao, Hui Su, Ziyu Guo, Yu Meng, Yixiao Xiong, Zhili Deng and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  2. Article
  3. Research progress on the mechanism of FOXO protein in sepsis.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. 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

16 authors.

Qian ZhouDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Yuming SunDepartment of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Songtao DuDepartment of Colorectal Surgical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province 150000, China.
Yating DianDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Lei YaoDepartment of General Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Hui SuDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Ziyu GuoDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Yu MengDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Yixiao XiongDepartment of Dermatology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, Hubei, China.
Zhili DengDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratary of Aging Biology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Xinwei KuangDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Xiaowei LiangDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Hong LiuDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Guangtong DengDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China. Electronic address: dengguangtong@outlook.com.
Xiang ChenDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Furong Laboratory, 87 Xiangya Road, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 87 Xiangya Road, Changsha 410008, Hunan Province, China. Electronic address: chenxiangck@126.com.
Furong ZengDepartment of Oncology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China. Electronic address: zengflorachn@hotmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunotherapy has revolutionized cancer treatment, yet challenges persist, such as resistance and lethal thromboembolism, necessitating dual-purpose strategies. Targeting ferroptosis emerges as a promising strategy to enhance immunotherapy efficacy, prompting our investigation of antiplatelet agents that simultaneously promote ferroptosis and mitigate thromboembolic risks. Through systematic screening of 20 Food and Drug Administration (FDA)-approved antiplatelet agents, we identify vorapaxar as a potent pro-ferroptotic drug. Mechanistically, vorapaxar binds forkhead box O1 (FOXO1), inhibits its phosphorylation at Ser256, and facilitates nuclear translocation to upregulate heme oxygenase 1 (HMOX1), promoting mitochondrial iron overload and mitochondria-associated ferroptosis. Vorapaxar enhances immunotherapy-induced tumor ferroptosis and antitumor immunity across diverse melanoma models, including B16F10 tumor-bearing mice, Braf/Pten-driven spontaneous melanoma mice, and peripheral blood mononuclear cell (PBMC)-humanized mice. Clinically, high FOXO1/HMOX1 co-expression correlates with improved immunotherapy response and progression-free survival. These findings position vorapaxar as a promising adjunct to immunotherapy, offering a dual benefit for cancer patients requiring both antithrombotic therapy and immunotherapy.

Indexed as

FerroptosisForkhead Box Protein O1Heme Oxygenase-1ImmunotherapyMitochondriaPyridinesAnimalsCell Line, TumorHumansMelanoma, ExperimentalMiceMice, Inbred C57BLSignal TransductionForkhead Box Protein O1FOXO1 protein, humanHeme Oxygenase-1PyridinesferroptosisFOXO1HMOX1immunotherapyvorapaxar

Identifiers

PMID41005298
PMCPMC12629800

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.