Evidence map›Paper›PMID 40931551›Full record

ArticleCancer biology & medicine2025

A novel biguanide-derivative promotes NEDD4-mediated FGFR1 ubiquitination through BMI1 to overcome osimertinib resistance in NSCLC.

Mei Peng, Weifan Wang, Di Xiao, Duo Li, Jun Deng, Hui Zou, Xing Feng, Yunhai Yang, Songqing Fan, Xiaoping Yang

Abstract read
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In one paragraph

Article in Cancer biology & medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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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

10 authors.

Mei PengDepartment of Pharmacy and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
Weifan WangDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.
Di XiaoDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.
Duo LiDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.
Jun DengDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.
Hui ZouDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.
Xing FengDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.
Yunhai YangDepartment of Oncological Surgery, Shanghai Chest Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.ORCID 0000-0001-9848-3845
Songqing FanDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.ORCID 0000-0002-1486-9909
Xiaoping YangDepartment of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, China.ORCID 0000-0003-1952-7227

Funding

Key Project of Developmental Biology and Breeding from Hunan Province 2022XKQ0205National Natural Science Foundation of China 82172653National Natural Science Foundation of China 82472728Natural Science Foundation of Hunan Province 2025JJ80150Research Team for Reproduction Health and Translational Medicine of Hunan Normal University 2023JC101
6 · The paper itself

Abstract

objectiveOsimertinib (OSI) therapy, a cornerstone in treating non-small cell lung cancer (NSCLC), has been severely limited by rapidly developing acquired resistance. Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance. Biguanides, with excellent anti-tumor effects, have recently attracted much attention for this potential. The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.

methodsA comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI. Proteomics, co-immunoprecipitation mass spectrometry, RNA sequencing, and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy. NSCLC tumor tissues, especially OSI-resistant tissues, obtained from our clinic were used to assess the correlations between key proteins and OSI resistance.

resultsSMK-010, a highly potent biguanide compound, effectively overcame OSI resistance

conclusionsThese findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide, SMK-010, in combination with OSI.

Indexed as

AcrylamidesAniline CompoundsBiguanidesCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmLung NeoplasmsNedd4 Ubiquitin Protein LigasesReceptor, Fibroblast Growth Factor, Type 1AnimalsCell Line, TumorFemaleHumansIndolesMicePyrimidinesUbiquitinationAcrylamidesAniline CompoundsBiguanidesFGFR1 protein, humanIndolesNedd4 protein, humanNedd4 Ubiquitin Protein LigasesosimertinibPyrimidinesReceptor, Fibroblast Growth Factor, Type 1biguanideBMI1FGFR1 ubiquitinationNSCLCosimertinib resistance

Identifiers

PMID40931551
PMCPMC12624813

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