Evidence map›Paper›PMID 42049705›Full record

ArticleCell death & disease2026

Direct coupling and protective activation of DRP1 by the DNA-PKcs inhibitor KU-57788 synergizes with ferroptosis in anaplastic thyroid cancer cells.

Lingling Ding, Changtian Yin, Yehao Guo, Qiang Geng, Wanwan He, Yawen Guo, Jinpeng Wen, Aoni Zhou, Jieyu Luo, Xinxin Ren and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Lingling Ding *Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Changtian Yin *Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Yehao Guo *Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Qiang Geng *Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Wanwan HeOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Yawen GuoOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-9575-4192
Jinpeng WenPostgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Provincial People's Hospital), Wenzhou, Zhejiang, China.
Aoni ZhouThe Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Jieyu LuoThe Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Xinxin RenOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0008-8376-3690
Jiajie XuOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Renhao OuOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Ruonan JiaOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Jiaxin TianOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Yuchen WangOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Yefeng CaiOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-8751-2556
Wenzhen WangKey Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.ORCID http://orcid.org/0009-0005-4447-9767
Haifeng XuDepartment of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0009-3298-0051
Lei ZhuDepartment of Thyroid Surgery, The Fifth Hospital Affiliated to Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, China.
Minghua GeOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. geminghua@hmc.edu.cn.
Guowan ZhengOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. zhengguowan@hmc.edu.cn.ORCID http://orcid.org/0000-0001-5731-8325
Chuanming ZhengOtolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. mingdoc@163.com.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82273287National Natural Science Foundation of China (National Science Foundation of China) 82372618National Natural Science Foundation of China (National Science Foundation of China) 82403142Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LQ22H160063
6 · The paper itself

Abstract

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies, with limited treatment options and poor clinical outcomes. KU-57788, a selective inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), has shown promise in cancer therapy when combined with radiotherapy and chemotherapy. However, its therapeutic potential and underlying mechanisms in ATC remain unclear. In this study, we demonstrate that KU-57788 exerts potent anti-ATC activity both in vitro and in vivo by inducing DNA damage and triggering mitotic catastrophe. Unexpectedly, we identify a novel mechanism whereby KU-57788 directly binds to and activates dynamin-related protein 1 (DRP1), leading to excessive mitochondrial fission and fragmentation. This process is accompanied by the protective activation of the NRF2/SLC7A11/GSH axis, which mitigates the cytotoxic effects of KU-57788. Notably, pharmacological induction of ferroptosis or cystine depletion effectively synergizes with ATC cells to KU-57788, overcoming resistance and promoting ferroptosis. Collectively, our findings highlight the therapeutic potential of KU-57788 in ATC while revealing an intrinsic resistance mechanism mediated by DRP1 activation and the potential involvement of the NRF2/SLC7A11/GSH axis. More importantly, we provide strong evidence that combining KU-57788 with ferroptosis inducers significantly enhances its anticancer efficacy, offering a promising therapeutic strategy for ATC.

Indexed as

DNA-Activated Protein KinaseDynaminsFerroptosisMorpholinesPyronesThiophenesThyroid Carcinoma, AnaplasticThyroid NeoplasmsAnimalsCell Line, TumorHumansMiceMice, NudeMitochondrial DynamicsNF-E2-Related Factor 2DNA-Activated Protein KinaseDNM1L protein, humanDynaminsMorpholinesNF-E2-Related Factor 2PyronesThiophenes

Identifiers

PMID42049705
PMCPMC13265778

What Socratic 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 Socratic graph.