Genes & Cancer

Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor

Luyao Wang1, Lin Wang1, Magdalena Cybula1, Ana Luiza Drumond-Bock1, Katherine M. Moxley2 and Magdalena Bieniasz1

1 Oklahoma Medical Research Foundation, Oklahoma, OK, USA

2 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Oklahoma Health Science Center, Oklahoma, OK, USA


Magdalena Bieniasz, email:

Keywords: AD80, ovarian cancer, PDX, sfRon, multi-kinase inhibitor

Received: March 06, 2020 Accepted: July 17, 2020 Published: July 22, 2020


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.

PII: 205