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Background: Research on mortality outcomes and non-cancer-related causes of death in patients with malignant brain tumors remains limited. This study aims to identify the prevalence of non-cancer-related causes of death after brain cancer (BC) diagnosis. Methods: Data of patients diagnosed with BC in the USA between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were retrieved and analyzed. Standardized mortality ratios (SMRs) were calculated for all the reported causes of death. Results: A total of 59,663 deaths were reported during the follow-up period. The highest number of fatalities (34,677) occurred within the first year following BC diagnosis. BC-attributable deaths were the leading cause of mortality (55,482; 93%), followed by non-cancer deaths (3888; 6.5%). BC patients had an increased risk of non-cancer attributable deaths (SMR = 6.12; 95% CI 5.93–6.31) including heart diseases (N = 938; SMR = 5.3; 95% CI 4.96–5.65), cerebrovascular diseases (N = 453; SMR = 13.17; 95% CI 11.98–14.44), accidents and adverse effects (N = 227; SMR = 2.97; 95% CI 2.6–3.39), and septicemia (N = 155; SMR = 13.39; 95% CI 11.36–15.67). Conclusion: Compared to the general population, BC patients had a statistically significant higher risk of death from most of the reported causes. [ABSTRACT FROM AUTHOR]

In the past few years, basic and clinical scientists have witnessed landmark achievements in many research projects, such as those conducted by the US National Institutes of Health Roadmap Epigenomics Mapping Consortium, the International Human Epigenome Consortium, The Cancer Genome Atlas Network and the International Cancer Genome Consortium, which have provided near-complete resolution of epigenetic landscape in different diseases. Furthermore, genome sequencing of tumors has provided compelling evidence related to frequent existence of mutations in readers, erasers and writers of epigenome in different cancers. Histone acetylation is an intricate mechanism modulated by two opposing sets of enzymes and deeply studied as a key biological phenomenon in 1964 by Vincent Allfrey and colleagues. The research group suggested that this protein modification contributed substantially in transcriptional regulation. Subsequently, histone deacetylases (HDACs), histone acetyltransferases and acetyl-Lys-binding proteins were identified as transcriptional mediators, which further deepened our comprehension regarding biochemical modifications. Overwhelmingly increasing high-impact research is improving our understanding of this molecularly controlled mechanism; moreover, quantification and identification of lysine acetylation by mass spectrometry has added new layers of information. We partition this multi-component review into how both activity and expression of HDAC are targeted using natural agents. We also set spotlight on how oncogenic fusion proteins tactfully utilize HDAC-associated nano-machinery to modulate expression of different genes and how HDAC inhibitors regulate TRAIL-induced apoptosis in cancer cells. HDAC inhibitors have been reported to upregulate expression of TRAIL receptors and protect TRAIL from proteasomal degradation. Deeper understanding of HDAC biology will be useful for stratification and selection of patients who are responders, non-responders and poor-responders for HDACi therapy, and for the rational design of combination studies using HDACi. [ABSTRACT FROM AUTHOR]