Abstract 5605: Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas

• Published in: Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.5605-5605
• Main Authors: Miao, Benchun, Zhang, Jianming, Ji, Zhenyu, Njauw, Ching Ni, Taylor, Michael, Kumar, Raj, Gray, Nathanael, Tsao, Hensin
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-5605

The Eph receptors are the largest known family of receptor tyrosine kinases (RTKs). Research studies have shown that Eph receptors and ligands may be involved in many diseases including cancer. EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. Our previous studies showed that EphA2 levels are elevated in melanoma cells and EphA2 plays critical roles in melanoma cell survival, proliferation, colony formation and migration in vitro and melanoma tumor growth in vivo. Together, these data suggest that EphA2 is a critical oncogene in melanoma and a potential pharmacologic target in the treatment of metastatic disease. Herein we present early evidence that EphA2 inhibitors (ALW-II-41-27 and HG-6-64-1) are effective in inhibiting proliferation of both NRAS and BRAF mutant melanoma cell lines in vitro through suppressing a series of EphA2 downstream signaling pathways. At the same time, EphA2 inhibitors are also effective at suppressing migration and invasion of melanoma cells with a reduction in actin cytoskeleton reorganization and lamellipodia formation. Animal studies are underway to determine the effectiveness of these agents in suppressing melanoma tumor growth in vivo. These results point to EphA2 inhibition as a promising therapeutic strategy for both NRAS and BRAF mutant melanomas either singly or in combination with BRAF or MEK inhibitors currently in trial. Citation Format: Benchun Miao, Jianming Zhang, Zhenyu Ji, Ching Ni Njauw, Michael Taylor, Raj Kumar, Nathanael Gray, Hensin Tsao. Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5605. doi:10.1158/1538-7445.AM2013-5605