Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment.
Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment.
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推动基因组引导精准放射治疗的发展。
DOI：
10.3390/cancers15225314
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发表时间：
2023-11-07
期刊：
影响因子：
5.2
通讯作者：
Li, Yun R.
中科院分区：
文献类型：
--
作者：
Tam, Andrew;Mercier, Benjamin D.;Thomas, Reeny M.;Tizpa, Eemon;Wong, Irene G.;Shi, Juncong;Garg, Rishabh;Hampel, Heather;Gray, Stacy W.;Williams, Terence;Bazan, Jose G.;Li, Yun R.
遗传信息很少被纳入癌症患者的放射治疗建议中，尽管遗传信息现在已经被很好地建立起来，可以预测癌症的预后和对系统治疗的反应。随着越来越多的人获得和使用基因检测，肿瘤和生殖系基因数据有可能通过提高放射治疗的有效性和确保治疗的安全性而为临床决策提供信息。本文综述了放射增敏基因的生物学基础，讨论了将基因突变识别为辐射反应生物标志物的临床基础和证据，并提出了未来研究和临床应用的方向。放射治疗(RT)是多种癌症的主要治疗方法。根据患者的肿瘤病理、分期、解剖和其他临床特征，对每个患者的放疗和放射治疗计划进行个性化的建议。关于胚系突变和体细胞肿瘤突变的信息目前很少用于指导RT的特定临床决定。许多基因，如ATM和BRCA1/2，已经在实验室中被发现具有辐射敏感性。然而，我们对这些基因突变的临床意义的了解仍然有限，而且由于这些基因的个别突变可能很罕见，它们对肿瘤反应和毒性的影响仍不清楚。目前的指南，包括国家癌症综合网络(NCCN)的指南，对如何将遗传结果纳入RT建议提供了有限的指导。随着人们对放射反应的分子基础的了解日益加深，基因组引导的RT可以为围绕RT剂量、体积、同时治疗甚至遗漏而做出的决定提供信息，以进一步改善肿瘤学结果并降低毒性风险。在这里，我们回顾了实验室、临床前和临床研究中关于基因改变如何影响放射敏感性的现有证据。我们还总结了临床试验的最新数据，并探索了利用遗传数据支持临床决策的潜在未来方向，以开发一条走向个性化RT的途径。
Genetic information is seldom incorporated in formulating radiation treatment recommendations for patients with cancer, even though genetic information is now well established to be prognostic and predictive of cancer outcomes and response to systemic therapy. With the increasing accessibility to and use of genetic testing, tumor, and germline genetic data have the potential to inform clinical decisions by improving the efficacy of radiation treatment and ensuring the safety of treatment delivery. This review summarizes the biological underpinning of “radio-sensitizing genes”, discusses the clinical basis and evidence for identifying genetic mutations as radiation response biomarkers, and proposes future directions for research as well as clinical implementation. Radiation treatment (RT) is a mainstay treatment for many types of cancer. Recommendations for RT and the radiation plan are individualized to each patient, taking into consideration the patient’s tumor pathology, staging, anatomy, and other clinical characteristics. Information on germline mutations and somatic tumor mutations is at present rarely used to guide specific clinical decisions in RT. Many genes, such as ATM, and BRCA1/2, have been identified in the laboratory to confer radiation sensitivity. However, our understanding of the clinical significance of mutations in these genes remains limited and, as individual mutations in such genes can be rare, their impact on tumor response and toxicity remains unclear. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN), provide limited guidance on how genetic results should be integrated into RT recommendations. With an increasing understanding of the molecular underpinning of radiation response, genomically-guided RT can inform decisions surrounding RT dose, volume, concurrent therapies, and even omission to further improve oncologic outcomes and reduce risks of toxicities. Here, we review existing evidence from laboratory, pre-clinical, and clinical studies with regard to how genetic alterations may affect radiosensitivity. We also summarize recent data from clinical trials and explore potential future directions to utilize genetic data to support clinical decision-making in developing a pathway toward personalized RT.
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影响因子：
2.8
作者：
Wang, Hetong;Xie, Haitao;Wang, Shuying;Zhao, Jiaying;Gao, Ya;Chen, Jun;Zhao, Yuxia;Guo, Genyan
通讯作者：
Guo, Genyan
影响因子：
--
作者：
Fang Z;Kozlov S;McKay MJ;Woods R;Birrell G;Sprung CN;Murrell DF;Wangoo K;Teng L;Kearsley JH;Lavin MF;Graham PH;Clarke RA
通讯作者：
Clarke RA
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
3.6
作者：
Baskar R;Lee KA;Yeo R;Yeoh KW
通讯作者：
Yeoh KW
影响因子：
4.6
作者：
Tomioka K;Miyamoto T;Akutsu SN;Yanagihara H;Fujita K;Royba E;Tauchi H;Yamamoto T;Koh I;Hirata E;Kudo Y;Kobayashi M;Okada S;Matsuura S
通讯作者：
Matsuura S