Abstract 3913: Selective targeting of circulating tumor cells with agonistic EphA2 ligand

EphA2 is a tyrosine kinase receptor that is overexpressed in many cancer types like pancreatic, colon and breast cancers. Targeting cancer cells with an EphA2-targeting molecule conjugated with cytotoxic agents can spare normal cells from chemotherapy side effects. Here, we developed (123B9)2, a novel, potent ligand for the EphA2 receptor that binds to EphA2 ligand-binding domain and causes receptor activation at a sub micromolar concentration as evident in biochemical and cell-based assays. Furthermore, our molecule showed enhanced resistance to degradation, making it suitable for in vivo studies. Subsequently, we conjugated (123B9)2 with paclitaxel, a mitotic spindle inhibitor, and administered it in nude mice bearing breast cancer cells MDA-MD-231 in mammary glands. Remarkably, (123B9)2 paclitaxel-conjugate showed significant inhibition of breast cancer circulating tumor cells (CTC)s in orthotropic mice compared to paclitaxel alone. Finally, we are planning to use our molecule as a single agent to target cancer cells. Citation Format: Ahmed F. Salem, Si Wang, Sandrine Billet, Jie-Fu Chen, Parima Udompholkul, Luca Gambini, Carlo Baggio, Edwin M. Posadas, Neil A. Bhowmick, Maurizio Pellecchia. Selective targeting of circulating tumor cells with agonistic EphA2 ligand [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3913.