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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cycle Arrest; Metaanalysis; Repression; Diverse
ISSN (print) / ISBN 2639-5274
e-ISSN 2639-5274
Zeitschrift Research
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 0576 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Shanghai Municipal Science and Technology Major Project
National Natural Science Foundation of China
National Key Research and Development Program of China