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Abstract：
DNA-targeted drugs constitute a specialized category of pharmaceuticals developed for cancer treatment, directly influencing various cellular processes involving DNA. These drugs aim to enhance treatment efficacy and minimize side effects by specifically targeting molecules or pathways crucial to cancer growth. Unlike conventional chemotherapeutic drugs, recent discoveries have yielded DNA-targeted agents with improved effectiveness, and a new generation is anticipated to be even more specific and potent. The sequencing of the human genome in 2001 marked a transformative milestone, contributing significantly to the advancement of targeted therapy and precision medicine. Anticipated progress in precision medicine is closely tied to the continuous development in the exploration of synthetic lethality, DNA repair, and expression regulatory mechanisms, including epigenetic modifications. The integration of technologies like circulating tumor DNA (ctDNA) analysis further enhances our ability to elucidate crucial regulatory factors, promising a more effective era of precision medicine. The combination of genomic knowledge and technological progress has led to a surge in clinical trials focusing on precision medicine. These trials utilize biomarkers for identifying genetic alterations, molecular profiling for potential therapeutic targets, and tailored cancer treatments addressing multiple genetic changes. The evolving landscape of genomics has prompted a paradigm shift from tumor-centric to individualized, genome-directed treatments based on biomarker analysis for each patient. The current treatment strategy involves identifying target genes or pathways, exploring drugs affecting these targets, and predicting adverse events. This review highlights strategies incorporating DNA-targeted drugs, such as PARP inhibitors, SLFN11, methylguanine methyltransferase (MGMT), and ATR kinase.
摘要：
DNA靶向药物是为癌症治疗而开发的一类专门药物，直接影响涉及DNA的各种细胞过程。这些药物旨在通过特异性靶向对癌症生长至关重要的分子或途径来增强治疗功效并最小化副作用。与常规化疗药物不同,最近的发现已经产生了具有改善效力的DNA靶向药物，新一代预计将更加具体和有效。2001年的人类基因组测序标志着一个变革的里程碑，为靶向治疗和精准医学的发展做出了重要贡献。精准医学的预期进展与合成杀伤力探索的不断发展密切相关，DNA修复,和表达调节机制，包括表观遗传修饰。循环肿瘤DNA（ctDNA）分析等技术的整合进一步增强了我们阐明关键调节因子的能力，有望迎来更有效的精准医学时代。基因组知识和技术进步的结合导致了专注于精准医学的临床试验激增。这些试验利用生物标志物来识别遗传改变，潜在治疗靶点的分子谱分析，以及针对多种基因变化的量身定制的癌症治疗方法。基因组学不断发展的格局促使了从以肿瘤为中心到个性化的范式转变，基于每个患者的生物标志物分析的基因组导向治疗。目前的治疗策略包括确定靶基因或途径，探索影响这些靶点的药物，并预测不良事件。这篇综述强调了结合DNA靶向药物的策略，如PARP抑制剂，SLFN11,甲基鸟嘌呤甲基转移酶(MGMT),和ATR激酶。
