Figure 4.

Radiation-induced epigenetic alterations. A phenotypic switch during radiation treatment, leads several epigenetic modifications in the tumor cells. In fact, DNA methylation has been the most studied mechanism in RT resistance. Changes in DNA methylation did not occur uniformly into the cell genome. It has been described IR-induced specific methylated genes as TP53, CDKN1C and RUNX3, among others, in EC, resulting in uncontrolled cell cycle checkpoints and tumor growth. Additionally, PTMs, such as histone acetylation and/or methylation are also deregulated after IR treatment to promote cancer progression and development. Accordingly, there is a dynamic balance between tumor suppressor genes and oncogenes, resulting in lower apoptosis and higher cell proliferation and consequently, poor RT response. Abbreviations: Ac—acetylation; CDKN1C—cyclin dependent kinase inhibitor 1C; DNMTs—DNA methyltransferases; HDAC—histone deacetylases; IR—ionizing radiation; RT—radiotherapy; RUNX3—runt related transcription factor 3; TP53—tumor protein p53.