{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:30:06Z","timestamp":1786624206476,"version":"build-2736575974"},"reference-count":174,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573434"],"award-info":[{"award-number":["82573434"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82573434"],"award-info":[{"award-number":["82573434"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2023206263"],"award-info":[{"award-number":["H2023206263"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Esophageal cancer is a common malignancy of the upper gastrointestinal tract that is associated with high incidence and mortality rates. Radiotherapy constitutes a cornerstone therapeutic modality for esophageal cancer. In radiotherapy, ionizing radiation is used to eliminate tumor cells through direct DNA damage and indirect reactive oxygen species (ROS)-mediated effects. However, clinical outcomes are frequently limited by interpatient heterogeneity and intrinsic tumor radioresistance. This review systematically describes the determinants of radiosensitivity in esophageal cancer within the established radiobiological framework of the \u201c6Rs\u201d: DNA damage repair (Repair), which is mediated by \u03b3-H2AX phosphorylation, PARP family enzymes, and nonhomologous end joining (NHEJ) and homologous recombination (HR) pathways; cell cycle redistribution (Redistribution), which is regulated by G1\/S and G2\/M checkpoint dynamics; tumor repopulation (Repopulation), which is driven by cancer stem cell activity during fractionated treatment; reoxygenation (Reoxygenation), which is modulated through HIF-1\u03b1 signaling and ROS homeostasis; intrinsic radiosensitivity (Radiosensitivity), which reflects interindividual and histopathological variability; and reactivation of antitumor immune responses (Reactivation), which enhances efficacy by remodeling the tumor immune microenvironment. Furthermore, regulated cell death mechanisms, including ferroptosis, autophagy, and apoptosis, significantly modulate radiotherapeutic responses. Elucidating these interconnected mechanisms provides a robust theoretical foundation for developing targeted interventions, identifying predictive biomarkers, and advancing precision radiotherapy strategies to optimize clinical outcomes for patients with esophageal cancer.<\/jats:p>","DOI":"10.3390\/cancers18162610","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:33:46Z","timestamp":1786620826000},"page":"2610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms for Enhancing Radiosensitivity in Esophageal Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Dongli","family":"Guo","sequence":"first","affiliation":[{"name":"Cancer Institute, Fourth Hospital of Hebei Medical University, 12 Health Road, Chang\u2019an District, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"Cancer Institute, Fourth Hospital of Hebei Medical University, 12 Health Road, Chang\u2019an District, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Su","sequence":"additional","affiliation":[{"name":"Cancer Institute, Fourth Hospital of Hebei Medical University, 12 Health Road, Chang\u2019an District, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Institute, Fourth Hospital of Hebei Medical University, 12 Health Road, Chang\u2019an District, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpeng","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Radiation, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"He","sequence":"additional","affiliation":[{"name":"Cancer Institute, Fourth Hospital of Hebei Medical University, 12 Health Road, Chang\u2019an District, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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