AI Article Synopsis
- Epithelial ovarian cancer (EOC) is a highly lethal cancer due to late diagnosis and recurring drug resistance, prompting the need for innovative treatments.
- TWIST, a transcription factor associated with cancer progression and resistance, is identified as a promising target for therapy.
- The study shows that TWIST siRNA delivered by nanoparticles can effectively reduce drug resistance and tumor burden in EOC, suggesting a potential strategy for managing metastatic and resistant cancers.
Article Abstract
Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance, making it a promising therapeutic target. In this work, we demonstrate the efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to reverse chemoresistance in EOC models. Polyamidoamine dendrimers and mesoporous silica nanoparticles (MSNs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with cisplatin plus MSN-siTWIST exhibited lower tumor burden than mice treated with cisplatin alone, with most of the effect coming from reduction in disseminated tumors. This platform has potential application for overcoming the clinical challenges of metastasis and chemoresistance in EOC and other TWIST overexpressing cancers.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004794 | PMC |
| http://dx.doi.org/10.1016/j.nano.2016.11.010 | DOI Listing |
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