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Updated: Nov 20, 2025
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor
Luyao Wang1, Lin Wang1, Magdalena Cybula1
1Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Abstract:
The sfRon kinase is an important therapeutic target in ovarian cancer that contributes to prominent tumor growth and disease progression. We reasoned that a multi-kinase inhibition of sfRon pathway might be an effective strategy to achieve a sustained anti-tumor response, while simultaneously preventing treatment resistance. We performed a detailed dissection of sfRon signaling in vitro and demonstrated that S6K1 is a key component of a multi-kinase targeting strategy in sfRon expressing ovarian tumors. We selected AD80 compound that targets several kinases within sfRon pathway including AKT and S6K1, and compared its efficacy with inhibitors that selectively target either sfRon or PI3 kinase. Using human ovarian xenografts and clinically relevant patient-derived xenografts (PDXs), we demonstrated that in vivo treatment with single agent AD80 shows superior efficacy to a standard-care chemotherapy (cisplatin/paclitaxel), or to the direct inhibition of sfRon kinase by BMS777607. Our findings indicate that ovarian tumors expressing sfRon are most effectively treated with multi-kinase inhibitors simultaneously targeting AKT and S6K1, such as AD80, which results in long-term anti-tumor response and prevents metastasis development.
Insights
Multi-kinase inhibition targeting sfRon, AKT, and S6K1 with AD80 shows superior efficacy in ovarian cancer models. This approach offers a sustained anti-tumor response and prevents metastasis, outperforming current treatments.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- sfRon kinase drives ovarian cancer growth and progression.
- Targeting sfRon signaling is a potential therapeutic strategy.
- Developing resistance to single-target therapies necessitates novel approaches.
Purpose of the Study:
- To investigate a multi-kinase inhibition strategy for sfRon-expressing ovarian tumors.
- To evaluate the efficacy of AD80, a multi-kinase inhibitor, in preclinical ovarian cancer models.
- To compare AD80 with single-target inhibitors and standard chemotherapy.
Main Methods:
- In vitro analysis of sfRon signaling pathways.
- In vivo studies using human ovarian xenografts and patient-derived xenografts (PDXs).
- Treatment with AD80, selective sfRon inhibitor (BMS777607), PI3 kinase inhibitor, and cisplatin/paclitaxel chemotherapy.
Main Results:
- S6K1 was identified as a key component in sfRon signaling.
- AD80 demonstrated superior in vivo efficacy compared to standard chemotherapy (cisplatin/paclitaxel).
- AD80 showed better outcomes than direct sfRon inhibition by BMS777607.
Conclusions:
- Multi-kinase inhibitors like AD80, targeting AKT and S6K1 simultaneously, are effective against sfRon-expressing ovarian tumors.
- This strategy provides a sustained anti-tumor response and prevents metastasis.
- AD80 represents a promising therapeutic agent for ovarian cancer treatment.
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