Zhou, X.* ; Zhu, X.* ; Wang, W. ; Wang, J.* ; Wen, H.* ; Zhao, Y.* ; Zhang, J.* ; Xu, Q.* ; Zhao, Z.* ; Ni, T.*
Comprehensive cellular senescence evaluation to aid targeted therapies.
Research 8:0576 (2025)
Drug resistance to a single agent is common in cancer-targeted therapies, and rational drug combinations are a promising approach to overcome this challenge. Many Food and Drug Administration-approved drugs can induce cellular senescence, which possesses unique vulnerabilities and molecular signatures. However, there is limited analysis on the effect of the combination of cellular-senescence-inducing drugs and targeted therapy drugs. Here, we conducted a comprehensive evaluation of cellular senescence using 7 senescence-associated gene sets. We quantified the cellular senescence states of ~10,000 tumor samples from The Cancer Genome Atlas and examined their associations with targeted drug responses. Our analysis revealed that tumors with higher cellular senescence scores exhibited increased sensitivity to targeted drugs. As a proof of concept, we experimentally confirmed that etoposide-induced senescence sensitized lung cancer cells to 2 widely used targeted drugs, erlotinib and dasatinib. Furthermore, we identified multiple genes whose dependencies were associated with senescence status across ~1,000 cancer cell lines, suggesting that cellular senescence generates unique vulnerabilities for therapeutic exploitation. Our study provides a comprehensive overview of drug response related to cellular senescence and highlights the potential of combining senescence-inducing agents with targeted therapies to improve treatment outcomes in lung cancer, revealing novel applications of cellular senescence in targeted cancer therapies.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Cycle Arrest; Metaanalysis; Repression; Diverse
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Language
english
Publication Year
2025
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0
HGF-reported in Year
2025
ISSN (print) / ISBN
2639-5274
e-ISSN
2639-5274
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Article Number: 0576
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American Association for the Advancement of Science (AAAS)
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1200 New York Ave, Nw, Washington, Dc 20005 Usa
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Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503800-001
Grants
Shanghai Municipal Science and Technology Major Project
National Natural Science Foundation of China
National Key Research and Development Program of China
Copyright
Erfassungsdatum
2025-03-20