ARTICLE | Distillery Therapeutics

Therapeutics: EPH receptor A2 (EPHA2); BRAF

January 29, 2015 8:00 AM UTC

Cell culture, mouse and patient studies suggest inhibiting EPHA2 could help treat melanoma that is resistant to the BRAF inhibitor Zelboraf vemurafenib. In metastatic lesions from melanoma patients on Zelboraf therapy, EPHA2 levels were elevated after drug resistance emerged compared with pretreatment baselines in the same patients. In Zelboraf-resistant human melanoma cell lines, EPHA2 knockdown or small molecule EPHA2 inhibitors decreased proliferation compared with Zelboraf. In mouse xenograft mouse models of Zelboraf-resistant melanoma, the EPHA2 inhibitors decreased tumor growth compared with a Zelboraf analog. Next steps include studying patients in clinical trials of BRAF/MEK inhibitor combination therapy to look for associations between EPHA2 levels in tumors and either treatment failure or the prevention of metastasis.

Daiichi Sankyo Co. Ltd. and Roche market the BRAF inhibitor Zelboraf vemurafenib to treat melanoma. ...