BioCentury
ARTICLE | Distillery Therapeutics

Cancer

July 17, 2018 5:40 PM UTC

Patient sample, cell culture and mouse studies suggest inhibiting EZH2 or promoting FOXC1 expression could help treat the luminal B subtype of metastatic breast cancer. In patients with luminal B-type breast cancer, low tumor levels of FOXC1 correlated with high tumor levels of EZH2, and the low tumor levels of FOXC1 were associated with poor relapse-free survival. In two human luminal B-type metastatic breast cancer cell lines, overexpression of FOXC1 decreased invasiveness compared with normal FOXC1 expression. In a mouse model of luminal B-type metastatic breast cancer, mammary epithelium-specific knockout of EZH2 decreased the size and number of lung metastases and increased survival compared with normal EZH2 expression. In another mouse model of luminal B-type metastatic breast cancer, a tool compound EZH2 inhibitor decreased the number of lung metastases compared with vehicle. In a patient-derived xenograft (PDX) mouse model of luminal B-type metastatic breast cancer, the EZH2 inhibitor decreased the number of lung metastases. Next steps include elucidating the roles of FOXC1- and EZH2-regulated genes in the models.

Epizyme Inc. and Eisai Co. Ltd. have tazemetostat (E7438, EPZ-6438), an EZH2 inhibitor, in Phase II testing to treat B cell lymphoma, lymphoma, mesothelioma, non-Hodgkin’s lymphoma (NHL), sarcoma and solid tumors...

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