Marrer Estelle, Dieterle Frank
Novartis Institutes for BioMedical Research, Translational Sciences, Novartis, Klybeckstr. 141, CH-4002 Basel, Switzerland.
Expert Opin Drug Metab Toxicol. 2008 Nov;4(11):1391-402. doi: 10.1517/17425255.4.11.1391.
Oncology is considered as the pioneer indication for the clinical application of molecular biomarkers. Newly developed targeted anticancer therapies call for the implementation of molecular biomarker strategies but even novel cytotoxic treatments use biomarkers for the assessment of efficacy and toxicity. Biomarkers may play several roles in the progression of a drug from research to personalised medicine. In particular biomarkers are used to understand the mechanism of action of a drug, monitor the modulation of the intended target, assess efficacy and safety, adapt dosing and schedule, select patients and prognosticate the clinical outcome. Nowadays, the use of biomarkers in oncology is still challenged as only a limited number of oncology drugs on the market have a companion biomarker test to be mandatorily performed before treatment. This is in contradiction with the current major investment the pharmaceutical sector is devoting to biomarker identification and development. What are the measurable milestones and outcomes of these investments? How does biomarker development contribute to reaching the ultimate goal of finding the right molecules for the right targets at the right doses and schedules for the right patients? This review provides a critical overview of recent salient achievements in the identification and development of biomarkers.
肿瘤学被视为分子生物标志物临床应用的先驱领域。新开发的靶向抗癌疗法需要实施分子生物标志物策略，甚至新型细胞毒性治疗也使用生物标志物来评估疗效和毒性。生物标志物在药物从研发到个性化医疗的进程中可能发挥多种作用。特别是，生物标志物可用于了解药物的作用机制、监测预期靶点的调节、评估疗效和安全性、调整给药剂量和方案、选择患者以及预测临床结果。如今，肿瘤学中生物标志物的应用仍面临挑战，因为市场上只有少数肿瘤药物有配套的生物标志物检测，需要在治疗前强制进行。这与制药行业目前在生物标志物识别和开发方面的大量投入相矛盾。这些投资的可衡量里程碑和成果是什么？生物标志物的开发如何有助于实现为合适的患者在合适的剂量和方案下找到针对合适靶点的合适分子这一最终目标？本综述对生物标志物识别和开发方面的近期显著成就进行了批判性概述。
