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Failures are driven mainly by local or regional recurrence rather than distant metastasis, making local control critical. At the cellular level, ionizing radiation primarily damages DNA, while signaling and repair networks determine whether lesions are repaired or lead to apoptosis. Tumor defects in DNA repair, particularly involving p53, EGFR, and p16-mediated pathways, can support radiosensitivity, enabling biomarker-guided prognosis and personalized treatment strategies and informing immunotherapy combinations.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dna-damage-response-and-potential-biomarkers-of-radiosensitivity-in-head-and-neck-cancers-clinical-implications/381238/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dna-damage-response-and-potential-biomarkers-of-radiosensitivity-in-head-and-neck-cancers-clinical-implications/381238.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is local control emphasized in head and neck cancer radiotherapy?","Question",{"text":112,"@type":113},"Because treatment failures are mainly due to recurrences and local or regional evolution, with distant metastases being less common. This makes maintaining local control a key goal.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does DNA damage relate to radiotherapy-induced cell death?",{"text":117,"@type":113},"Radiotherapy primarily targets deoxyribonucleic acid (DNA), and DNA lesions largely drive radiation-induced cell death. The biological outcome depends on which damage is repaired and which signaling and repair pathways remain functional.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biomarkers and pathways are highlighted for radiosensitivity assessment?",{"text":121,"@type":113},"The review focuses on mechanisms involving p53, epidermal growth factor receptor (EGFR), and p16, and discusses DNA damage-associated biomarkers for clinical selection of personalized treatments and prognosis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},381238,1790966295,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","REVIEW  \nR J M E  \nRomanian Journal of Morphology & Embryology  \n[http://www.rjme.ro/](http://www.rjme.ro/)  \nDNA damage response and potential biomarkers of radiosensitivity in head and neck cancers: clinical implications  \nDOMNICA CARPOV1), RAREŞ BUIGĂ1–3), VIORICA-MAGDALENA NAGY1,3)  \n1) Department of Radiotherapy, Prof. Dr. Ion Chiricuţă Oncology Institute, Cluj-Napoca, Romania  \n2) Department of Pathology, Prof. Dr. Ion Chiricuţă Oncology Institute, Cluj-Napoca, Romania  \n3)Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania  \nAbstract  \nHead and neck cancers include a wide variety of tumor sites that originate in the epithelium of the upper aerodigestive airways. The curative treatment of this group of pathologies most frequently involves multidisciplinary approach in which radiotherapy (RT) plays a central role. Treatment failures are mainly due to recurrences and local or regional evolution and rarely to distant metastases, which emphasizes the importance of ensuring local control. For patients with recurrences, the treatment options are significantly reduced, and prognosis is considerably attenuated. At the cellular level, the main irradiation target is the deoxyribonucleic acid (DNA), its lesions being largely responsible for radiationinduced cell death. However, not all DNA damage will have the same biological significance and a considerable part will be repaired through an intricate network of signaling proteins and repair pathways. Radiobiologically, compared to normal cells, tumor clonogens are defined by malfunction of DNA repair pathways. Tumors with an increased repair capacity, especially DNA double-strand breaks, the most lethal lesions induced by RT, will be radioresistant. The purpose of this review was to elucidate the mechanisms involved in avoiding radiation-induced apoptosis of head and neck cancers mediated by modulating the repair of DNA damage via p53, epidermal growth factor receptor (EGFR) and p16 . The role of DNA damage-associated biomarkers in response to irradiation in clinical practice for the selection of personalized treatments and specifying the prognosis and, finally, the bases of immunotherapy association are presented.  \nKeywords: DNA damage, DNA repair, head and neck cancer, radiotherapy , biomarkers.  \n􀀕 Introduction  \nHead and neck cancers include a wide variety of tumor sites that originate in the epithelium of the upper aerodigestive tract. With an incidence of over 900 000 new cases worldwide annually, it ranks 7th among the most common tumor locations [1] .  \nThe topographic location influences the spread and prognosis, but at the same time there is a series of common elements in terms of etiology, histogenesis, evolution, prognosis, and response to treatment [2, 3] .  \nThe most important etiological factors are common to all locations and include smoking, chronic alcoholism, poor oral hygiene, chewing betel leaves, and more recently documented, inhalation of E-cigarette vapors and human papillomavirus (HPV) infection, which imprint certain prognostic features [4] .  \nThe evolution is mainly loco-regional. Treatment failures are primarily due to recurrences or local or regional evolution (70%) and rarely to metastases (30%), which emphasizes the importance of obtaining local control.  \nTraditionally, establishment the treatment considers only the clinical prognostic factors – category tumor (T), lymph node (N)–, staging according to American Joint Committee on Cancer (AJCC), pathological prognostic factors–pTNM–and performance status, so that patients  \nin the same stage category benefit from the same therapeutic strategy [5] . However, due to the molecular pathways responsible for the still incompletely elucidated malignant phenotype, offering similar treatments to patients in identical stage categories is associated with significantly different prognostic outcomes [6](Figures 1 and 2). The therapeutic index could be improved by clinical integration and ada","cbCairjZjKxfdvTM","https://ap.wps.com/l/cbCairjZjKxfdvTM","pdf",2012301,"English","# Abstract\n# Introduction\n## Epidemiology and common etiologic factors\n## Treatment failure patterns and clinical prognostic factors\n## Precision biomarkers and radiosensitivity biology\n# Radiotherapy in multimodal management\n# Open-access license information\n# Figures","[{\"question\":\"Why is local control emphasized in head and neck cancer radiotherapy?\",\"answer\":\"Because treatment failures are mainly due to recurrences and local or regional evolution, with distant metastases being less common. This makes maintaining local control a key goal.\"},{\"question\":\"How does DNA damage relate to radiotherapy-induced cell death?\",\"answer\":\"Radiotherapy primarily targets deoxyribonucleic acid (DNA), and DNA lesions largely drive radiation-induced cell death. The biological outcome depends on which damage is repaired and which signaling and repair pathways remain functional.\"},{\"question\":\"Which biomarkers and pathways are highlighted for radiosensitivity assessment?\",\"answer\":\"The review focuses on mechanisms involving p53, epidermal growth factor receptor (EGFR), and p16, and discusses DNA damage-associated biomarkers for clinical selection of personalized treatments and prognosis.\"}]","DNA damage response and potential biomarkers of radiosensitivity in head and neck cancers: clinical implications | PDF",1790244353,23]