DNA double-strand break repair in cancer: A path to achieving precision medicine.
DNA double-strand break repair in cancer: A path to achieving precision medicine.
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DOI：
10.1016/bs.ircmb.2021.06.003
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发表时间：
2021
影响因子：
--
通讯作者：
Davis J
中科院分区：
文献类型：
--
作者：
Gillyard T;Davis J
DNA损伤的评估是精准医学的重要诊断手段。癌症中的DNA双链断裂（DSBs）途径是大多数抗癌疗法的主要靶点，然而每种肿瘤背后的分子脆弱性可能差异很大，这使得精准医学的应用具有挑战性。识别和理解这些个体间的脆弱性，可以设计靶向DSB抑制剂，以及不断发展的精准医学方法，以最小的副作用选择性地杀死癌细胞。然而，一个主要的挑战是如何准确地定义DSB修复途径机制中的独特差异。这篇综述包括对癌症中DSB修复机制的简要概述，包括通过CRISPR/Cas9和机器学习/人工智能等革命性进展获得的结果，这些进展不仅迅速推进了我们对DSB修复选择决定因素的理解，而且还促进了如何将其用于推进精准医学。用于诊断和治疗癌症的方法的科学创新正在与基础科学和转化研究的进步相融合。这场革命将继续成为精准医疗的关键驱动力，精准医疗将使独特的个体机制成为可能。本文旨在为实现这一目标奠定基础。
The assessment of DNA damage can be a significant diagnostic for precision medicine. DNA double strand break (DSBs) pathways in cancer are the primary targets in a majority of anticancer therapies, yet the molecular vulnerabilities that underlie each tumor can vary widely making the application of precision medicine challenging. Identifying and understanding these interindividual vulnerabilities enables the design of targeted DSB inhibitors along with evolving precision medicine approaches to selectively kill cancer cells with minimal side effects. A major challenge however, is defining exactly how to target unique differences in DSB repair pathway mechanisms. This review comprises a brief overview of the DSB repair mechanisms in cancer and includes results obtained with revolutionary advances such as CRISPR/Cas9 and machine learning/artificial intelligence, which are rapidly advancing not only our understanding of determinants of DSB repair choice, but also how it can be used to advance precision medicine. Scientific innovation in the methods used to diagnose and treat cancer is converging with advances in basic science and translational research. This revolution will continue to be a critical driver of precision medicine that will enable precise targeting of unique individual mechanisms. This review aims to lay the foundation for achieving this goal.
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