AI Article Synopsis
- Ovarian cancer is the most deadly gynecological cancer, with current chemotherapy often ineffective due to drug resistance, especially in advanced stages.
- A new treatment using a nanoformulation called Bola/IM targets ovarian cancer stem cells (CSCs) more effectively than imatinib alone, utilizing a specific mechanism to inhibit cancer growth and spread.
- The Bola/IM formulation shows promising results in lab models and enhances the effectiveness of cisplatin, making it a strong candidate for improving treatment for metastatic ovarian cancer.
Article Abstract
Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.
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| http://dx.doi.org/10.1021/acsami.4c12857 | DOI Listing |
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