A Perspective of Epigenetic Regulation in Radiotherapy.
A Perspective of Epigenetic Regulation in Radiotherapy.
复制标题
DOI：
10.3389/fcell.2021.624312
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Peng Q;Weng K;Li S;Xu R;Wang Y;Wu Y
放射治疗（RT）作为一种杀肿瘤方式已经有100多年的历史，在美国每年有47万例患者接受放射治疗。电离辐射引起遗传变化并导致细胞死亡。然而，由于辐射的生物学机制尚不清楚，因此迫切需要了解这种机制，以提高对肿瘤的杀伤效果并减少对正常细胞的副作用。放疗可引起DNA断裂和表观遗传重构。因此，组蛋白修饰酶的调节可以调节癌细胞的放射敏感性。例如，组蛋白去乙酰化酶（HDAC）抑制剂通过放大DNA损伤信号传导和抑制双链DNA断裂修复来敏化照射的癌细胞以影响照射的细胞的存活。然而，表观遗传药物和放射疗法的组合仅在几项正在进行的临床试验中对有限的癌症类型进行了评估，部分原因是缺乏对辐射如何诱导表观遗传调节和染色质重塑的潜在机制的了解。本文综述了放射治疗和放射治疗诱导的表观遗传重构的最新进展，并介绍了表观遗传监测的相关技术。特别是，我们利用荧光共振能量转移（FRET）生物传感器的应用，可视化动态表观遗传调控在单个活细胞和组织后，放疗和药物治疗。我们的目标是连接FRET生物传感器，表观遗传学和放射治疗，提供一个使用FRET评估表观遗传学的角度，并为放射治疗提供指导，以改善癌症治疗。最后，我们讨论了表观遗传药物和放射治疗相结合作为癌症治疗新方法的可行性。
Radiation therapy (RT) has been employed as a tumoricidal modality for more than 100 years and on 470,000 patients each year in the United States. The ionizing radiation causes genetic changes and results in cell death. However, since the biological mechanism of radiation remains unclear, there is a pressing need to understand this mechanism to improve the killing effect on tumors and reduce the side effects on normal cells. DNA break and epigenetic remodeling can be induced by radiotherapy. Hence the modulation of histone modification enzymes may tune the radiosensitivity of cancer cells. For instance, histone deacetylase (HDAC) inhibitors sensitize irradiated cancer cells by amplifying the DNA damage signaling and inhibiting double-strand DNA break repair to influence the irradiated cells’ survival. However, the combination of epigenetic drugs and radiotherapy has only been evaluated in several ongoing clinical trials for limited cancer types, partly due to a lack of knowledge on the potential mechanisms on how radiation induces epigenetic regulation and chromatin remodeling. Here, we review recent advances of radiotherapy and radiotherapy-induced epigenetic remodeling and introduce related technologies for epigenetic monitoring. Particularly, we exploit the application of fluorescence resonance energy transfer (FRET) biosensors to visualize dynamic epigenetic regulations in single living cells and tissue upon radiotherapy and drug treatment. We aim to bridge FRET biosensor, epigenetics, and radiotherapy, providing a perspective of using FRET to assess epigenetics and provide guidance for radiotherapy to improve cancer treatment. In the end, we discuss the feasibility of a combination of epigenetic drugs and radiotherapy as new approaches for cancer therapeutics.
登录
查看更多内容
DOI：
10.1016/j.bbamcr.2007.07.002
发表时间：
2007-10-01
影响因子：
5.1
作者：
Falk, Martin;Lukasova, Emilie;Kozubek, Stanislav
通讯作者：
Kozubek, Stanislav
DOI：
10.1016/j.mrfmmm.2011.10.006
发表时间：
2012-03-01
影响因子：
2.3
作者：
Abou-El-Ardat, Khalil;Monsieurs, Pieter;Baatout, Sarah
通讯作者：
Baatout, Sarah
影响因子：
158.5
作者：
DiNardo, C. D.;Stein, E. M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
DOI：
10.1073/pnas.1221312110
发表时间：
2013-04-16
影响因子：
11.1
作者：
Choi, Paul J.;Mitchison, Timothy J.
通讯作者：
Mitchison, Timothy J.
影响因子：
12.3
作者：
Dillon SC;Zhang X;Trievel RC;Cheng X
通讯作者：
Cheng X