Development and use of biomarkers in oncology drug development.
Development and use of biomarkers in oncology drug development.
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DOI：
10.1080/01926230490425021
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发表时间：
2004-03-01
影响因子：
1.5
通讯作者：
McShane, Teresa M
中科院分区：
文献类型：
--
作者：
Floyd, Eugenia;McShane, Teresa M
生物标志物的成功开发和使用将提高肿瘤药物开发的生产力。 NIH 工作组提出的精确定义和概念反映了对生物标志物对加速药物开发重要性的认识，该工作组旨在标准化术语并促进采用更加连贯和系统的方法来开发和使用生物标志物。药物疗效的潜在临床生物标志物通常通过临床前研究或基础研究来确定。随着临床成像技术（尤其是分子和功能成像）的不断进步，用于肿瘤学的潜在生物标志物的鉴定正在迅速向前发展。其他快速进步是用于现有技术的新科学试剂的不断增加以及高通量基因组和蛋白质组技术的产物，这些技术可以产生数百种潜在的生物标志物以供进一步评估。在某些情况下，传统的临床诊断技术或测定可以适用于临床前模型，以评估其作为生物标志物预测新候选药物的临床反应的能力。潜在生物标志物的评估（临床前和临床）通常是生物标志物开发的最长阶段，评估或验证的标准取决于预期用途和临床开发阶段。经验证可用于临床前研究的生物标志物可用于帮助选择合适的动物模型和先导化合物。经过验证可用于临床试验的生物标志物可以确认药物的药理学或生物学作用机制，指导方案设计，帮助患者和剂量选择，并有助于最大程度地降低安全风险。可以通过使用一组分层的临床生物标志物来优化肿瘤药物开发，这些临床生物标志物可以预测化合物的功效和安全性，并随着层数的增加而增加信心，从而帮助企业做出有关推进化合物的决策。在肿瘤学中，一类经过广泛评估的特殊疗效生物标志物（替代终点）通常与所需的临床结果相关，可用作公司决策以及加速药物临时监管批准的基础。
Successful development and use of biomarkers will improve the productivity of oncology drug development. Recognition of the importance of biomarkers for speeding drug development is reflected in the precise definitions and concepts proposed by an NIH Working Group to standardize terminology and promote a more coherent and systematic approach to the development and use of biomarkers. Potential clinical biomarkers of drug efficacy are often identified through pre-clinical studies or basic research. Identification of potential biomarkers for use in oncology is moving rapidly forward through continuing advances in clinical imaging technologies, especially molecular and functional imaging. Other rapid advances are a product of the growing availability of new scientific reagents for established technologies and of high-throughput genomic and proteomic technologies that can generate hundreds of potential biomarkers for further evaluation. In certain cases, conventional clinical diagnostic techniques or assays can be adapted for use in pre-clinical models to evaluate their ability to serve as biomarkers for predicting clinical responses to new drug candidates. Evaluation (pre-clinical and clinical) of a potential biomarker is often the longest stage of biomarker development, and standards for evaluation or validation depend on the intended use and stage of clinical development. Biomarkers verified for use in preclinical studies can be used to help select appropriate animal models and lead compounds. Biomarkers verified for use in clinical trials can confirm a drug's pharmacological or biological mechanism of action, guide protocol design, aid patient and dose selection, and help to minimize safety risks. Oncology drug development can be optimized by using a tiered set of clinical biomarkers that predict compound efficacy and safety with increasing confidence at each rise in tier thereby aiding corporate decision-making about advancing compounds. In oncology, a special class of extensively evaluated biomarkers of efficacy (surrogate endpoints) that generally correlate with desired clinical outcomes can be used as a basis for corporate decisions as well as for gaining accelerated provisional regulatory approval of a drug.