Therapeutics: Histone deacetylase (HDAC); DNA (cytosine-5-)-methyltransferase 1 (DNMT1)

Patient sample, cell and mouse studies suggest combining inhibitors of HDAC and DNMT1 could help treat breast cancer. In human and mouse breast cancer cell lines, an HDAC inhibitor tool compound plus the DNMT1 inhibitor Vidaza azacitidine decreased proliferation and colony formation compared with either agent alone. In luminal progenitor and basal stem cells from primary mouse breast tumors, the combination decreased proliferation of cancer stem cells (CSCs) and formation of tumorspheres. In a mouse model of breast cancer, the combination therapy increased survival compared with vehicle. Next steps could include testing the combination in other cancers.

Celgene Corp., Nippon Shinyaku Co. Ltd. and Pfizer Inc. market Vidaza to treat myelodysplastic syndrome (MDS). Celgene and Pfizer also market Vidaza to treat acute myelogenous leukemia (AML) and have the compound in Phase I/II testing to treat chronic lymphocytic leukemia (CLL) and Phase I testing to treat B cell lymphoma. ...