{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGAGE2E, a member of the cancer/testis antigen family, has been identified as a key mediator of radiotherapy resistance in cervical cancers. Elevated expression of this antigen is associated with innate resistance to radiotherapy, suggesting its potential as a predictive biomarker. This discovery underscores the significant role that GAGE2E plays in tumor aggressiveness and treatment failure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistically, the GAGE protein, particularly the GAGE12 variant, enhances radiotherapy resistance through a synemin-dependent mechanism that promotes its localization to chromatin. This positioning facilitates the recruitment of histone deacetylases HDAC1 and HDAC2 to the inhibitor actin, leading to increased acetylation of histone 3 on lysine 56 (H3K56Ac). Consequently, chromatin becomes more accessible, thereby improving the efficiency of DNA repair processes that counteract radiotherapy-induced damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, these findings highlight the potential utility of GAGE2E as a pre-screening biomarker for identifying patients likely to exhibit poor responses to radiotherapy. Furthermore, the study presents a compelling case for the development of molecular or pharmacological agents designed to disrupt the GAGE-associated complex, which could restore sensitivity to radiotherapy and ultimately improve treatment outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dawn Sijin Nin, Caryn Wujanto, Tuan Zea Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109621"}], "href": "https://doi.org/10.1016/j.celrep.2021.109621"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34469741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34469741"}]}]}]}