Superenhancers as master gene regulators and novel therapeutic targets in brain tumors

Transcriptional deregulation, a cancer cell hallmark, is driven by epigenetic abnormalities in the majority of brain tumors, including adult glioblastoma and pediatric brain tumors. Epigenetic abnormalities can activate epigenetic regulatory elements to regulate the expression of oncogenes. Superenhancers (SEs), identified as novel epigenetic regulatory elements, are clusters of enhancers with cell-type specificity that can drive the aberrant transcription of oncogenes and promote tumor initiation and progression. As gene regulators, SEs are involved in tumorigenesis in a variety of tumors, including brain tumors. SEs are susceptible to inhibition by their key components, such as bromodomain protein 4 and cyclin-dependent kinase 7, providing new opportunities for antitumor therapy. In this review, we summarized the characteristics and identification, unique organizational structures, and activation mechanisms of SEs in tumors, as well as the clinical applications related to SEs in tumor therapy and prognostication. Based on a review of the literature, we discussed the relationship between SEs and different brain tumors and potential therapeutic targets, focusing on glioblastoma. Brain cancer: opportunities to block “super-enhanced” tumor growth “Superenhancer” regions within the genome help coordinate the malignant growth of brain tumors, and could offer a target for the development of therapies and prognostic biomarkers. These regions contain a dense accumulation of gene regulatory sequences, which operate in collaboration to establish cellular identity. A review by Jian Qu and colleagues at Central South University, Changsha, China, shows how these regulatory sequences get hijacked in various brain cancers and can facilitate tumor cell proliferation and invasion. Many tumor cells acquire mutations that lead to the formation of superenhancers that are absent in healthy cells. However, this process also offers therapeutic opportunities, and researchers have identified numerous drug candidates that can potentially block tumorigenesis by selectively interfering with superenhancer function. Superenhancer activity could also provide a potentially useful clinical signature for assessing tumor aggressiveness.