C5aR1和cGAS/STING及其可能参与癌症的放射敏感性
C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.
摘要(中文译文)
在全球范围内，结直肠癌（CRC）在诊断和死亡率方面均位居第三大癌症，凸显了其对全球健康的重大影响。利用放射增敏剂（如C5aR1（补体C5a受体1）阻断）增强放疗，在治疗耐药性CRC方面显示出前景，尤其是在免疫冷肿瘤中。然而，C5aR1抑制提高放射敏感性的分子机制仍有待阐明。cGAS/STING（环鸟苷酸-腺苷酸合成酶/干扰素基因刺激因子）通路活性降低与放射抵抗相关，而放疗诱导的cGAS/STING激活可增加IFNB1（干扰素β1）并损害DNA修复。相反，补体成分5a（C5a）/C5aR1轴在免疫反应中抑制STING驱动的IFNB1表达，提示它们对癌细胞放疗反应具有不同的调控作用。因此，靶向C5aR1可能通过调节cGAS/STING通路来增强放射敏感性。本综述探讨了C5aR1与cGAS/STING通路之间潜在的相互作用，强调它们与解决CRC耐药机制的相关性。
Abstract
Worldwide, colorectal cancer (CRC) stands as the third leading cancer in terms of both diagnosis and mortality, underscoring its significant global health impact. Enhancing radiotherapy with radiosensitizers, such as C5aR1 (complement C5a receptor 1) blockade, has shown promise in treating resistant CRC, particularly in immunologically cold tumors. However, the molecular mechanisms by which C5aR1 inhibition improves radiosensitivity remain to be clarified. Reduced cGAS/STING (cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon genes) pathway activity is linked to radioresistance, while radiotherapy-induced cGAS/STING activation increases IFNB1 (interferon beta 1) and impairs DNA repair. Conversely, the complement component 5a (C5a)/C5aR1 axis suppresses STING-driven IFNB1 expression in immune responses, suggesting their distinct regulatory effects on cancer cell radiotherapy responses. Targeting C5aR1 may therefore enhance radiosensitivity by modulating the cGAS/STING pathway. This review examines potential interactions between C5aR1 and the cGAS/STING pathway, highlighting their relevance to addressing resistance mechanisms in CRC.
如何引用
AMA
Quoc Thao Trang Pham, Pei-Ju Lee, Nguyen Quoc Khanh Le. C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.. iScience. 2026; doi:10.1016/j.isci.2026.115009.
APA
Quoc Thao Trang Pham, Pei-Ju Lee, Nguyen Quoc Khanh Le (2026). C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.. iScience. https://doi.org/10.1016/j.isci.2026.115009
GB/T 7714
Quoc Thao Trang Pham, Pei-Ju Lee, Nguyen Quoc Khanh Le. C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.[J]. iScience, 2026 doi:10.1016/j.isci.2026.115009.
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