Section of Translational Medical Sciences, Division of Applied Medicine, School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom.
Eur J Cancer. 2010 Mar;46(5):869-79. doi: 10.1016/j.ejca.2010.01.001.
A priority translational research objective in cancer medicine is the discovery of novel therapeutic targets for solid tumours. Ideally, co-discovery of predictive biomarkers occurs in parallel to facilitate clinical development of agents and ultimately personalise clinical use. However, the identification of clinically useful predictive biomarkers for solid tumours has proven challenging with many initially promising biomarkers failing to translate into clinically useful applications. In particular, the 'failure' of a predictive biomarker has often only become apparent at a relatively late stage in investigation. Recently, the field has recognised the need to develop a robust clinical biomarker development methodology to facilitate the process. This review discusses the recent progress in this area focusing on the key stages in the biomarker development process: discovery, validation, qualification and implementation. Concentrating on predictive biomarkers for selecting systemic therapies for individual patients in the clinic, the advances and progress in each of these stages in biomarker development are outlined and the key remaining challenges are discussed. Specific examples are discussed to illustrate the challenges identified and how they have been addressed. Overall, we find that significant progress has been made towards a formalised biomarker developmental process. This holds considerable promise for facilitating the translation of predictive biomarkers from discovery to clinical implementation. Further enhancements could eventually be found through alignment with regulatory processes.
癌症医学的一个优先转化研究目标是发现实体瘤的新型治疗靶点。理想情况下，预测性生物标志物的共同发现应与促进药物的临床开发并行，最终实现临床应用的个体化。然而，已经证明，鉴定实体瘤的临床有用的预测性生物标志物具有挑战性，许多最初有希望的生物标志物未能转化为临床有用的应用。特别是，预测性生物标志物的“失效”通常只有在研究的相对后期才变得明显。最近，该领域已经认识到需要开发一种稳健的临床生物标志物开发方法学来促进这一过程。这篇综述讨论了这一领域的最新进展，重点介绍了生物标志物开发过程中的关键阶段：发现、验证、定性和实施。集中讨论了用于在临床中为个体患者选择全身治疗的预测性生物标志物，概述了生物标志物开发各个阶段的进展和进步，并讨论了关键的遗留挑战。讨论了具体的例子来说明确定的挑战以及如何解决这些挑战。总的来说，我们发现已经朝着正式的生物标志物开发过程取得了重大进展。这为将预测性生物标志物从发现转化为临床实施提供了很大的希望。通过与监管过程的一致性，最终可能会发现进一步的改进。
