Evidence map›Paper›PMID 42752668›Full record

ArticleCancer chemotherapy and pharmacology2026

Targeting ALDH2 with Alda-1 to reverse cisplatin resistance in lung adenocarcinoma.

Meidong Zhou, Fengjuan Tang, Zhiling Qu, Nan Luo, Sailong Ma, Xizhen Xu

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Article in Cancer chemotherapy and pharmacology, 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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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Meidong Zhou *Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095, Wuhan, 430030, China.
Fengjuan Tang *Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095, Wuhan, 430030, China.
Zhiling QuInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095, Wuhan, 430030, China.
Nan LuoSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Sailong MaInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095, Wuhan, 430030, China.
Xizhen XuInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095, Wuhan, 430030, China. xu_xizhen@126.com.

Funding

Technical Research Project Funding by Huazhong University of Science and Technology No.HZKJSYJSXM2024M100
6 · The paper itself

Abstract

backgroundCisplatin resistance remains a major obstacle in lung adenocarcinoma (LUAD) treatment. The role of Aldehyde dehydrogenase 2 (ALDH2), a detoxifying enzyme, in LUAD prognosis and chemoresistance is poorly understood.

methodsWe analyzed ALDH2's prognostic value using clinical cohorts, TCGA, and proteomic data. Cisplatin-resistant cell lines and xenograft models were used to assess the effect of the ALDH2 agonist Alda-1. Molecular mechanisms were investigated via gain/loss-of-function studies.

resultsHigh ALDH2 expression was significantly associated with improved survival in univariate analysis and correlated with a favorable genomic instability profile in LUAD. Pharmacological activation of ALDH2 with Alda-1 restored cisplatin sensitivity in resistant cells and potently enhanced cisplatin's efficacy in vivo. Mechanistically, ALDH2 activation upregulated PKC-ζ, leading to downregulation of the drug efflux pump MDR1. Proteomic analysis further linked low ALDH2 expression to a pro-chemoresistance signature.

conclusionALDH2 represents a potential prognostic biomarker associated with favorable outcomes in LUAD, particularly in patients receiving chemotherapy. Its activation via Alda-1 overcomes cisplatin resistance by targeting the PKC-ζ/MDR1 axis, presenting a novel therapeutic strategy.

Indexed as

Adenocarcinoma of LungAldehyde Dehydrogenase, MitochondrialBenzodioxolesCisplatinDrug Resistance, NeoplasmLung NeoplasmsAnimalsAntineoplastic AgentsBenzamidesCell Line, TumorFemaleHumansMicePrognosisProteomicsXenograft Model Antitumor AssaysAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanAntineoplastic AgentsBenzamidesBenzodioxolesCisplatinN-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamideAlda-1ALDH2Cisplatin resistanceLung adenocarcinomaProteomic profiling

Identifiers

PMID42752668

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