Histone modifications in epigenetic regulation of cancer: Perspectives and achieved progress.

Histone deacetylases (HDAC) and histone deacetylase inhibitors (HDACi) have greatly impacted the war on cancer. Their role in epigenetics has significantly altered the development of anticancer drugs used to treat the most rare, persistent forms of cancer. During transcription, HDAC and HDACi are used to regulate the genetic mutations found in cancerous cells by removing and/or preventing the removal of the acetyl group on specific histones. This activity determines the relaxed or condensed conformation of the nucleosome, changing the accessibility zones for transcription factors. These modifications lead to other biological processes for the cell, including cell cycle progression, proliferation, and differentiation. Each HDAC and HDACi class or group has a distinctive mechanism of action that can be utilized to halt the progression of cancerous cell growth. While the use of HDAC- and HDACi-derived compounds are relatively new in treatment of cancers, they have a proven efficacy when the appropriately utilized. This following manuscript highlights the mechanisms of action utilized by HDAC and HDACi in various cancer, their role in epigenetics, current drug manufacturers, and the impact predicative modeling systems have on cancer therapeutic drug discovery.

https://www.mdpi.com/2079-9721/7/4/57/pdf

Histone Deacetylases and their Inhibitors in Cancer Epigenetics.

Small-molecule inhibitors of breast cancer-related targets: Potential therapeutic agents for breast cancer.

Metastasis is a complex process that involved in various genetic and epigenetic alterations during the progression of breast cancer. Recent evidences have indicated that the mutation in the genome sequence may not be the key factor for increasing metastatic potential. Epigenetic changes were revealed to be important for metastatic phenotypes transition with the development in understanding the epigenetic basis of breast cancer. Herein, we aim to present the potential epigenetic drivers that induce dysregulation of genes related to breast tumor growth and metastasis, with a particular focus on histone modification including histone acetylation and methylation. The pervasive role of major histone modification enzymes in cancer metastasis such as histone acetyltransferases (HAT), histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and so on are demonstrated and further discussed. In addition, we summarize the recent advances of next-generation sequencing technologies and microfluidic-based devices for enhancing the study of epigenomic landscapes of breast cancer. This feature also introduces several important biotechnologists for identifying robust epigenetic biomarkers and enabling the translation of epigenetic analyses to the clinic. In summary, a comprehensive understanding of epigenetic determinants in metastasis will offer new insights of breast cancer progression and can be achieved in the near future with the development of innovative epigenomic mapping tools.

/pdf/perspectives-on-the-role-of-histone-modification-in-breast-55qixh0ksv.pdf

Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis.

Xiaohui Li

Papers

Small molecule HDAC inhibitors: Promising agents for breast cancer treatment.