page_title: Epigenetic priming
section_title: Cancer
hierarchical_section_title: Epigenetic priming / Cancer
caption_attribution_description: Español: Sensitización de una célula cancerígena con priming epigenético.
context_page_description: Epigenetic priming is the modification to a cell's epigenome whereby specific chromatin domains within a cell are converted from a closed state to an open state, usually as the result of an external biological trigger or pathway, allowing for DNA access by transcription factors or other modification mechanisms. The action of epigenetic priming for a certain region of DNA dictates how other gene regulation mechanisms will be able to act on the DNA later in the cell’s life. Epigenetic priming has been chiefly investigated in neuroscience and cancer research, as it has been found to play a key role in memory formation within neurons and tumor-suppressor gene activation in cancer treatment respectively.
context_section_description: Epigenetic priming was first described in cancer research when epigenetic alterations on tumor-suppressor genes (TSG) were found to be drivers of carcinogenesis. Epigenetic alterations (e.g. DNA methylation) resulting in TSG inactivation as a common means of tumor formation. Contrary to regular DNA mutations common in cancer, methylation is reversible, provided that the chromatin is adequately open to allow hypomethylating agents to access the DNA and prevent methylation. Therefore, priming was investigated as a ‘pre-treatment’ to sensitize the tumerogenic cells to hypomethylating chemotheraputics such as decitabine. Many types of cancer (e.g. gastric) are known for having aberrant epigenetic changes, particularly in DNA methylation. In contrast to DNA mutations which cannot be easily changed through treatment, these aberrant epigenetic changes allow for a reversible treatment avenue.
  Epigenetic agents have proved to increase expression of aberrantly silenced genes (i.e. Runx3, Tnf, Pycard, Fas) in mice models after 5-aza-CR treatment . Thus, helping overcome cancer-induced cell dysfunction. Additionally, epigenetic priming has been shown to enhance cytotoxicity of cancer drugs (i.e. SN38 and CDDP), showing promising results in lung and ovarian cancer. Due to their proved effectivity, the FDA approved 5-azacytidine, romidepsin and other DMNT inhibitors (i.e. 5-azacytidine, hydralazine, 5-Aza-2’-deoxycytidine) and HDAC inhibitors (i.e. romidepsin, belinostat, panobinostat) for clinical use .
caption: Cancer cell sensitization to treatment through epigenetic priming. Normal cell with activated tumor suppressor genes (TSG) and Cancer cell with inactivated TSG through epigenetic mechanisms (showing only acetylation for simplification purposes). Priming stimuli performed with DNMT and/or HDAC inhibitors following by immunotherapy treatment (second stimuli) leading to reactivation of TSG.
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