Cell Signaling Pathways That Promote Radioresistance of Cancer Cells.
Cell Signaling Pathways That Promote Radioresistance of Cancer Cells.
复制标题
DOI：
10.3390/diagnostics12030656
复制
发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Yan Y
中科院分区：
文献类型：
--
作者：
Ouellette MM;Zhou S;Yan Y
放射治疗(RT)是实体瘤的标准治疗方法，大约50%的癌症患者，包括儿童癌症，接受放射治疗。虽然RT显著改善了癌症患者的总体生存和生活质量，但在相当数量的癌症患者(固有的或获得性的)中，其疗效仍然受到辐射抵抗的显著限制，导致对疾病的RT控制失败。辐射主要通过造成DNA损伤来根除癌细胞。然而，辐射也同时激活多条生存信号通路，其中包括ATM、ATR、AKT、ERK和NF-κB介导的那些促进DNA损伤检查点激活/DNA修复、自噬诱导和/或抑制细胞凋亡的信号通路。此外，新的数据支持YAP信号在促进癌细胞内在辐射抗性方面的作用，这是通过激活许多支持细胞生存、DNA修复、增殖和癌症干细胞的必需基因的转录而发生的。总之，这些信号通路通过降低辐射诱导的细胞毒性和促进辐射抗性来保护癌细胞。因此，靶向这些促生存信号通路可能会潜在地提高癌细胞的放射敏感性。在这篇综述中，我们总结了这些途径对癌细胞辐射抗性的贡献。
Radiation therapy (RT) is a standard treatment for solid tumors and about 50% of patients with cancer, including pediatric cancer, receive RT. While RT has significantly improved the overall survival and quality of life of cancer patients, its efficacy has still been markedly limited by radioresistance in a significant number of cancer patients (intrinsic or acquired), resulting in failure of the RT control of the disease. Radiation eradicates cancer cells mainly by causing DNA damage. However, radiation also concomitantly activates multiple prosurvival signaling pathways, which include those mediated by ATM, ATR, AKT, ERK, and NF-κB that promote DNA damage checkpoint activation/DNA repair, autophagy induction, and/or inhibition of apoptosis. Furthermore, emerging data support the role of YAP signaling in promoting the intrinsic radioresistance of cancer cells, which occurs through its activation of the transcription of many essential genes that support cell survival, DNA repair, proliferation, and the stemness of cancer stem cells. Together, these signaling pathways protect cancer cells by reducing the magnitude of radiation-induced cytotoxicity and promoting radioresistance. Thus, targeting these prosurvival signaling pathways could potentially improve the radiosensitivity of cancer cells. In this review, we summarize the contribution of these pathways to the radioresistance of cancer cells.
登录
查看更多内容
影响因子：
2.6
作者：
Dai, Xiao-Fang;Ding, Jie;Wu, Gang
通讯作者：
Wu, Gang
影响因子：
5.7
作者：
Dittmann, K;Mayer, C;Rodemann, HP
通讯作者：
Rodemann, HP
影响因子：
9.7
作者：
Chen, Benjamin P. C.;Li, Mengxia;Asaithamby, Aroumougame
通讯作者：
Asaithamby, Aroumougame
影响因子：
21.3
作者：
Bulavin, DV;Higashimoto, Y;Fornace, AJ
通讯作者：
Fornace, AJ
影响因子：
16
作者：
Cohen-Armon, Malka;Visochek, Leonid;Seger, Rony
通讯作者：
Seger, Rony