Defining the heterogeneous molecular landscape of lung cancer cell responses to epigenetic inhibition

HDAC inhibitors (HDACi) have been shown to exhibit powerful anticancer activities. However, cellular responses to HDAC inhibition are heterogenous and dependent on factors such as the genetic background, metabolic state, and on-/off-target engagement of individual HDACi drugs. To determine the mechanisms that drive these heterogeneous cellular responses, we quantified proteome remodeling of HDACi-treated cell lines derived from diverse genetic backgrounds. To do this, we utilized high-throughput sample multiplexed proteomics and integrated intelligent data acquisition methods to map proteomes of five cancer cell lines in response to HDACi. We found heterogeneous genetic backgrounds of cell lines can drive divergent cellular responses to HDACi.