Enhancer rewiring in tumors: an opportunity for therapeutic intervention

Enhancers are cis-regulatory sequences that fine-tune expression of their target genes in a spatiotemporal manner. They are recognized by sequence-specific transcription factors, which in turn recruit transcriptional coactivators that facilitate transcription by promoting assembly and activation of the basal transcriptional machinery. Their functional importance is underscored by the fact that they are often the target of genetic and nongenetic events in human disease that disrupt their sequence, interactome, activation potential, and/or chromatin environment. Dysregulation of transcription and addiction to transcriptional effectors that interact with and modulate enhancer activity are common features of cancer cells and are amenable to therapeutic intervention. Here, we discuss the current knowledge on enhancer biology, the broad spectrum of mechanisms that lead to their malfunction in tumor cells, and recent progress in developing drugs that efficaciously target their dependencies.