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Targeting ribonucleotide reductase for cancer therapy

机译：靶向核糖核苷酸还原酶用于癌症治疗

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Introduction: Ribonucleotide reductase (RR) is a unique enzyme, because it is responsible for reducing ribonucleotides to their corresponding deoxyribonucleotides, which are the building blocks required for DNA replication and repair. Dysregulated RR activity is associated with genomic instability, malignant transformation and cancer development. The use of RR inhibitors, either as a single agent or combined with other therapies, has proven to be a promising approach for treating solid tumors and hematological malignancies. Areas covered: This review covers recent publications in the area of RR, which include: i) the structure, function and regulation of RR; ii) the roles of RR in cancer development; iii) the classification, mechanisms and clinical application of RR inhibitors for cancer therapy and iv) strategies for developing novel RR inhibitors in the future. Expert opinion: Exploring the possible nonenzymatic roles of RR subunit proteins in carcinogenesis may lead to new rationales for developing novel anticancer drugs. Updated information about the structure and holoenzyme models of RR will help in identifying potential sites in the protein that could be targets for novel RR inhibitors. Determining RR activity and subunit levels in clinical samples will provide a rational platform for developing personalized cancer therapies that use RR inhibitors.
机译：简介：核糖核苷酸还原酶（RR）是一种独特的酶，因为它负责将核糖核苷酸还原为其相应的脱氧核糖核苷酸，而脱氧核糖核苷酸是DNA复制和修复所需的构件。 RR活性失调与基因组不稳定，恶性转化和癌症发展有关。 RR抑制剂作为单一药物或与其他疗法联合使用已被证明是治疗实体瘤和血液系统恶性肿瘤的一种有前途的方法。涵盖领域：这篇综述涵盖了《无线电规则》领域的最新出版物，包括：i）《无线电规则》的结构，功能和法规; ii）RR在癌症发展中的作用; iii）用于癌症治疗的RR抑制剂的分类，机理和临床应用，以及iv）将来开发新型RR抑制剂的策略。专家意见：探索RR亚基蛋白在致癌中可能的非酶作用可能会为开发新型抗癌药物提供新的理论依据。有关RR的结构和全酶模型的最新信息将有助于鉴定蛋白质中潜在的位点，这些位点可能是新型RR抑制剂的靶标。确定临床样品中的RR活性和亚基水平将为开发使用RR抑制剂的个性化癌症疗法提供一个合理的平台。

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