Histone proteins are a primary component of chromatin; therefore, any modifications to their structure are anticipated to affect the behavior of our genetic material, which is manifested in the form of phenotypic changes at a molecular, cellular or organic level. The majority of histone modifications are of either methylation or acetylation type that regulate gene expression. Though, not all of these modifications are concerned with the direct regulation of gene transcription. Throughout its 13-year run, Epigenomics has never ceased to cover these most gripping epigenetic stories, a significant proportion of which is in the matter of histones and their modifications. As such, the current perspective piece is intended to highlight original histone-oriented contributions published in Epigenomics since 2020.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, associated with poor survival outcomes. Lack of early diagnosis, resistance to conventional therapeutic treatments (including immunotherapy) and recurrence are some of the major hurdles in PDAC and contribute to its poor survival rate. While the risk of genetic predisposition to cancers is widely acknowledged and understood, recent advances in whole-genome and next-generation sequencing techniques have led to the acknowledgment of the role played by epigenetics, especially in PDAC. Epigenetic changes are heritable genetic modifications that influence gene expression without altering the DNA sequence. Epigenetic mechanisms (e.g., DNA methylation, post-translational modification of histone complexes and ncRNA) that result in reversible changes in gene expression are increasingly understood to be responsible for tumor initiation, development and even escape from immune surveillance. Our review seeks to highlight the various components of the epigenetic machinery that are known to be implicated in PDAC initiation and development and the feasibility of targeting these components to identify novel pharmacological strategies that could potentially lead to breakthroughs in PDAC treatment.