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ToolsSulaiman, Andrew, McGarry, Sarah, El-Sahli, Sara, Li, Li, Chambers, Jason, Phan, Alexandra, Côte, Marceline, Cron, Greg O., Alain, Tommy, Le, Yevgeniya, Lee, Seung Hwan, Liu, Sheng, Figeys, Daniel, Gadde, Suresh and Wang, Lisheng (2019) Co-targeting Bulk Tumor and CSCs in Clinically Translatable TNBC Patient-Derived Xenografts via Combination Nanotherapy. Molecular Cancer Therapeutics, 18 (10). pp. 1755-1764. ISSN 1535-7163
Full text not available from this repository. (Request a copy)Abstract
Triple-negative breast cancer (TNBC) accounts disproportionally for the majority of breast cancer–related deaths throughout the world. This is largely attributed to lack of a specific therapy capable of targeting both bulk tumor mass and cancer stem cells (CSC), as well as appropriate animal models to accurately evaluate treatment efficacy for clinical translation. Thus, development of effective and clinically translatable targeted therapies for TNBC is an unmet medical need. We developed a hybrid nanoparticles-based co-delivery platform containing both paclitaxel and verteporfin (PV-NP) to target TNBC patient-derived xenograft (PDX) tumor and CSCs. MRI and IVIS imaging were performed on mice containing PDX tumors to assess tumor vascularity and accumulation of NPs. NF-kB, Wnt, and YAP activities were measured by reporter assays. Mice bearing TNBC PDX tumor were treated with PV-NPs and controls, and tumors progression and CSC subpopulations were analyzed. MRI imaging indicated high vascularization of PDX tumors. IVIS imaging showed accumulation of NPs in PDX tumors. In comparison with control-NPs and free-drug combination, PV-NPs significantly retarded tumor growth of TNBC PDX. PV-NPs simultaneously repressed NF-kB, Wnt, and YAP that have been shown to be crucial for cancer growth, CSC development, and tumorigenesis. In conclusion, NPs containing two clinically used drugs concurrently inhibited NF-kB, Wnt, and YAP pathways and exhibited synergic effects on killing TNBC bulk tumor and CSCs. This combination nanotherapy evaluated with a PDX model may lead to an effective treatment of patients with TNBC.
| Item Type: | Article |
|---|---|
| Additional Information: | Publisher Copyright: ©2019 American Association for Cancer Research. |
| Uncontrolled Keywords: | oncology,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 26 Mar 2026 08:30 |
| Last Modified: | 29 Mar 2026 06:35 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/102582 |
| DOI: | 10.1158/1535-7163.MCT-18-0873 |
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