Establishment and characterization of 18 Sarcoma Cell Lines: Unraveling the Molecular Mechanisms of Doxorubicin Resistance in Sarcoma Cell Lines.
Cell lines
Doxorubicin
Drug resistance
Molecular profiling
Personalized medicine
Sarcoma
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
02 Oct 2024
02 Oct 2024
Historique:
received:
25
06
2024
accepted:
23
09
2024
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
2
10
2024
Statut:
epublish
Résumé
Sarcomas, malignant tumors from mesenchymal tissues, exhibit poor prognosis despite advancements in treatment modalities such as surgery, radiotherapy, and chemotherapy, with doxorubicin being a cornerstone treatment. Resistance to doxorubicin remains a significant hurdle in therapy optimization. This study aims to dissect the molecular bases of doxorubicin resistance in sarcoma cell lines, which could guide the development of tailored therapeutic strategies. Eighteen sarcoma cell lines from 14 patients were established under ethical approvals and classified into seven subtypes. Molecular, genomic, and transcriptomic analyses included whole-exome sequencing, RNA sequencing, drug sensitivity assays, and pathway enrichment studies to elucidate the resistance mechanisms. Variability in doxorubicin sensitivity was linked to specific genetic alterations, including mutations in TP53 and variations in the copy number of genomic loci like 11q24.2. Transcriptomic profiling divided cell lines into clusters by karyotype complexity, influencing drug responses. Additionally, pathway analyses highlighted the role of signaling pathways like WNT/BETA-CATENIN and HEDGEHOG in doxorubicin-resistant lines. Comprehensive molecular profiling of sarcoma cell lines has revealed complex interplays of genetic and transcriptomic factors dictating doxorubicin resistance, underscoring the need for personalized medicine approaches in sarcoma treatment. Further investigations into these resistance mechanisms could facilitate the development of more effective, customized therapy regimens.
Identifiants
pubmed: 39358756
doi: 10.1186/s12967-024-05700-y
pii: 10.1186/s12967-024-05700-y
doi:
Substances chimiques
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
889Subventions
Organisme : National Research Foundation of Korea
ID : 2021M3H9A1030151, 2022M3A9B6018217, NRF2022R1A5A102641311
Organisme : National Research Foundation of Korea
ID : 2021M3H9A1030151, 2022M3A9B6018217, NRF2022R1A5A102641311
Organisme : National Research Foundation of Korea
ID : 2021M3H9A1030151, 2022M3A9B6018217, NRF2022R1A5A102641311
Organisme : Korean Cell Line Research Foundation
ID : Korean Cell Line Research Foundation
Organisme : Korean Cell Line Research Foundation
ID : Korean Cell Line Research Foundation
Organisme : Korean Cell Line Research Foundation
ID : Korean Cell Line Research Foundation
Informations de copyright
© 2024. The Author(s).
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