Drug repurposing identifies proteasome inhibitors as antiproliferative agents counteracting inflammation-driven chemoresistance in triple-negative breast cancer organoids
2
Issued Date
2025-09-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-105010957813
Journal Title
Biomedicine and Pharmacotherapy
Volume
190
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.190 (2025)
Suggested Citation
Sari A.I.P., Roytrakul S., Chittavanich P., Saengwimol D., Laosillapacharoen N., Khamjerm J., Borwornpinyo S., Jinawath A., Suvikapakornkul R., Lertsithichai P., Chirappapha P., Jinawath N., Kaewkhaw R. Drug repurposing identifies proteasome inhibitors as antiproliferative agents counteracting inflammation-driven chemoresistance in triple-negative breast cancer organoids. Biomedicine and Pharmacotherapy Vol.190 (2025). doi:10.1016/j.biopha.2025.118359 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111387
Title
Drug repurposing identifies proteasome inhibitors as antiproliferative agents counteracting inflammation-driven chemoresistance in triple-negative breast cancer organoids
Corresponding Author(s)
Other Contributor(s)
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options, high relapse rates, and poor survival outcomes, largely due to chemoresistance. This study aimed to identify potential therapeutic strategies by repurposing FDA-approved anticancer drugs using patient-derived TNBC organoids from drug-resistant residual tumors post-chemotherapy. A high-throughput screen of 133 FDA-approved drugs, integrating image-based analysis and drug-sensitivity assays, identified the proteasome inhibitors bortezomib and carfilzomib as potent cytotoxic agents. Proteomic analysis, coupled with translation and cell cycle assays, showed that these inhibitors suppress TNBC organoid growth by downregulating ribosomal protein expression, leading to impaired translation and disrupted cell cycle progression. Furthermore, drug response dynamics confirmed their efficacy in overcoming clinical drug resistance. Transcriptomic profiling revealed that proteasome inhibitors counteract doxorubicin-induced, inflammation-driven resistance through dual anti-inflammatory and antiproliferative effects. Collectively, these findings support proteasome inhibition as a promising therapeutic strategy to overcome chemoresistance in TNBC.