Cancer

Cell culture and mouse studies suggest inhibiting EZH2 could help treat MYCN-driven neuroblastoma. In patients, low tumor expression of a MYCN-induced neuroblastoma gene signature comprising polycomb repressive complex 2 (PRC2) targets was associated with poor overall survival. In a MYCN-transformed mouse neuroblastoma cell line, knockdown of the PRC2 component EZH2 or the selective EZH2 inhibitor tazemetostat decreased tumorsphere formation compared with normal EZH2 expression or vehicle. In a mouse model of MYCN-driven neuroblastoma, tazemetostat decreased tumor growth compared with vehicle. Next steps could include testing EZH2 inhibitors in other models of neuroblastoma.

Epizyme Inc. and Eisai Co. Ltd. have tazemetostat (E7438, EPZ-6438), in Phase II testing to treat B cell lymphoma, lymphoma, mesothelioma, non-Hodgkin's lymphoma (NHL), sarcoma and solid tumors...