Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Ann Arbor, MI, 48109-1078, USA.
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Oncogene. 2020 Apr;39(18):3638-3649. doi: 10.1038/s41388-020-1250-3. Epub 2020 Mar 10.
Radiation is a significant treatment for patients with head and neck cancer. Despite advances to improve treatment, many tumors acquire radiation resistance resulting in poor survival. Radiation kills cancer cells by inducing DNA double-strand breaks. Therefore, radiation resistance is enhanced by efficient repair of damaged DNA. Head and neck cancers overexpress EGFR and have a high frequency of p53 mutations, both of which enhance DNA repair. This review discusses the clinical criteria for radiation resistance in patients with head and neck cancer and summarizes how cancer cells evade radiation-mediated apoptosis by p53- and epidermal growth factor receptor (EGFR)-mediated DNA repair. In addition, we explore the role of cancer stem cells in promoting radiation resistance, and how the abscopal effect provides rationale for combination strategies with immunotherapy.
辐射是治疗头颈部癌症患者的重要手段。尽管有多种方法可以提高治疗效果，但许多肿瘤仍会产生辐射抗性，导致生存率降低。辐射通过诱导 DNA 双链断裂来杀死癌细胞。因此，高效修复受损 DNA 会增强辐射抗性。头颈部癌症过度表达 EGFR，并且 p53 突变频率较高，这两者都增强了 DNA 修复。本文讨论了头颈部癌症患者辐射抗性的临床标准，并总结了癌细胞如何通过 p53 和表皮生长因子受体 (EGFR) 介导的 DNA 修复来逃避辐射诱导的细胞凋亡。此外，我们还探讨了癌症干细胞在促进辐射抗性中的作用，以及远隔效应如何为免疫疗法联合策略提供依据。
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