Histone Modifying Enzymes In Gynaecological Cancers

Simple SummaryEpigenetics is a process that allows genetic control, without the involvement of sequence changes to DNA or genes. In cancer, epigenetics is a key event in tumour development that can alter the expression of cancer driver genes and result in genomic instability. Due to the critical role of epigenetics in malignant transformation, therapies that target these processes have been developed to treat cancer. Here, we provide a summary of the epigenetic changes that have been described in a variety of gynaecological cancers. We then highlight how these changes are being targeted in preclinical models and clinical trials for gynaecological cancers.Genetic and epigenetic factors contribute to the development of cancer. Epigenetic dysregulation is common in gynaecological cancers and includes altered methylation at CpG islands in gene promoter regions, global demethylation that leads to genome instability and histone modifications. Histones are a major determinant of chromosomal conformation and stability, and unlike DNA methylation, which is generally associated with gene silencing, are amenable to post-translational modifications that induce facultative chromatin regions, or condensed transcriptionally silent regions that decondense resulting in global alteration of gene expression. In comparison, other components, crucial to the manipulation of chromatin dynamics, such as histone modifying enzymes, are not as well-studied. Inhibitors targeting DNA modifying enzymes, particularly histone modifying enzymes represent a potential cancer treatment. Due to the ability of epigenetic therapies to target multiple pathways simultaneously, tumours with complex mutational landscapes affected by multiple driver mutations may be most amenable to this type of inhibitor. Interrogation of the actionable landscape of different gynaecological cancer types has revealed that some patients have biomarkers which indicate potential sensitivity to epigenetic inhibitors. In this review we describe the role of epigenetics in gynaecological cancers and highlight how it may exploited for treatment.