Identification of Jun loss that promotes resistance to HDAC inhibitor Entinostat through Myc signaling in Luminal breast cancer (expression)

The histone deacetylase inhibitor Entinostat is in phase III trials for patients with metastatic estrogen receptor-positive breast cancer. Predictors of sensitivity and resistance, however, remain unknown. A total of 8 cell lines and 9 mouse models of breast cancer were treated with Entinostat. Luminal cell lines were treated with or without Entinostat at their IC50 doses, and MMTV/Neu luminal mouse tumors were treated with Entinostat until progression. We investigated these models using gene expression profiling by microarray and copy number by arrayCGH. We also utilized the network-based Dawnrank algorithm, that integrates DNA and RNA data, to identify driver genes of resistance. The impact of a number of candidate drivers was investigated in The Cancer Genome Atlas and the METABRIC