Evidence map›Paper›PMID 39716890›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer.

Ben Ma, Youzhou Sang, Xiaoxue Du, Yanzhi Zhang, Min Yin, Weibo Xu, Wanlin Liu, Jiayi Lu, Qing Guan, Yunjun Wang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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. Article
  2. Review
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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

19 authors.

Ben MaDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Youzhou SangDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China.
Xiaoxue DuDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Yanzhi ZhangDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Min YinDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Weibo XuDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Wanlin LiuDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Jiayi LuDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Qing GuanDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Yunjun WangDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Tian LiaoDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Yuting WangDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Jun XiangDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Rongliang ShiDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Ning QuDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Qinghai JiDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Jiwei ZhangThe MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P. R. China.
Dongmei JiDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China.
Yu WangDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.ORCID https://orcid.org/0000-0003-2622-294X

Funding

National Natural Science Foundation of China 82072951National Natural Science Foundation of China 82103666National Natural Science Foundation of China 82203052National Natural Science Foundation of China 82373315Science and Technology Commission of Shanghai Municipality 22Y21900100Shanghai Municipal Health Commission 20234Y0120
6 · The paper itself

Abstract

Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from thyroid follicular epithelium. Lenvatinib is an off-label use option for ATC patients in many countries but an approved prescription in Japan. However, lenvatinib resistance is a substantial clinical challenge. Clinical ATC samples including lenvatinib-resistant tumors are used to build patient-derived cells and patient-derived xenografts. High-throughput drug screening and synergy analyses are performed to identify an effective combination partner for lenvatinib. Cellular functions are detected by cell senescence, apoptosis, cell cycle, cell viability and colony formation assays. CDK2 inhibition showed the significant synthetic lethality with lenvatinib via inhibiting G1/S transition and inducing cell senescence in ATC. High expression of CDK2 is associated with lenvatinib resistance and poor clinical outcomes of ATC patients. Lenvatinib increased protein expression of CDK2 in lenvatinib-resistant ATC cells. Mechanistically, lenvatinib inhibited protein degradation of CDK2 via reducing CDK2's interaction with the RACK1-FBW7 complex, which is involved in ubiquitination and subsequent proteasomal degradation of CDK2. Combination of CDK2 inhibitors in clinical trials (Dinaciclib or PF-07104091) and lenvatinib markedly suppressed growth of xenograft tumors from the lenvatinib-resistant patient. The findings support the combination therapy strategy of lenvatinib and CDK2 inhibitor for lenvatinib-resistant ATC patients with high CDK2 expression.

Indexed as

Cellular SenescenceCyclin-Dependent Kinase 2Phenylurea CompoundsQuinolinesThyroid Carcinoma, AnaplasticThyroid NeoplasmsAnimalsAntineoplastic AgentsApoptosisCell Line, TumorDrug Resistance, NeoplasmHumansMiceProtein Kinase InhibitorsXenograft Model Antitumor AssaysAntineoplastic AgentsCDK2 protein, humanCyclin-Dependent Kinase 2lenvatinibPhenylurea CompoundsProtein Kinase InhibitorsQuinolinesATCCDK2DinaciclibFBW7PDXPF‐07104091

Identifiers

PMID39716890
PMCPMC11831524

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.