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However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment. Consequently, there is need for a comprehensive understanding of the regulatory mechanisms of tumor cells in response to radiation to improve radiotherapy efficacy. The current study aims to highlight new developments that illustrate various forms of cancer cell death after exposure to radiation. A summary of the cellular pathways and important target proteins that are responsible for tumor radioresistance and metastasis is also provided. Further, the study outlines several mechanistic descriptions of the interaction between ionizing radiation and the host immune system. Therefore, the current review provides a reference for future research studies on the biological effects of new radiotherapy technologies, such as ultra-high-dose-rate (FLASH) radiotherapy, proton therapy, and heavy-ion therapy.<\/jats:p>","DOI":"10.3390\/biom12091167","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T21:05:12Z","timestamp":1661288712000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Deciphering the Biological Effects of Radiotherapy in Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-5651","authenticated-orcid":false,"given":"Zhou","family":"Lu","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueting","family":"Zheng","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghe","family":"Ding","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Zou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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