Bough Kristopher J, Amur Shashi, Lao Guifang, Hemby Scott E, Tannu Nilesh S, Kampman Kyle M, Schmitz Joy M, Martinez Diana, Merchant Kalpana M, Green Charles, Sharma Jyoti, Dougherty Anne H, Moeller F Gerard
Division of Basic Neuroscience and Behavioral Research, National Institute on Drug Abuse, Bethesda, MD, USA.
Neuropsychopharmacology. 2014 Jan;39(1):202-19. doi: 10.1038/npp.2013.210. Epub 2013 Aug 27.
There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.
个性化药物研发已取得显著进展。在很大程度上，这一进展发生在肿瘤学领域，这得益于研究人员/临床医生发现和开发新型药物研发工具（DDTs）的能力，比如生物标志物。在癌症治疗研究中，生物标志物使对个体患者的病理生理特征描述更加准确，还使从业者能够在正确的时间，将正确的药物以正确的作用机制靶向正确的患者。与癌症类似，患有物质使用障碍（SUDs）的患者临床表现具有异质性症状，对治疗干预的反应也各不相同。如果能为物质使用障碍识别和开发出类似的生物标志物，那么在诊断和治疗方面可能会取得重大进展。在本综述中，我们重点介绍了目前在物质使用障碍生物标志物识别和开发方面的机遇与困难。我们以可卡因依赖为例进行阐述。我们将探讨一系列方法中可卡因依赖的推定诊断、药效学（PD）和预测性生物标志物。还将讨论一种可能的可卡因依赖临床结局评估（COA）——另一种定义的DDT。目前，可卡因依赖的生物标志物尚处于起步阶段。在这些推定工具可能用于药物研发和/或应用于临床实践之前，还需要进行大量额外研究来识别、验证和鉴定它们。然而，由于存在大量未满足的医疗需求，且估计每年市场规模达数亿美元，因此如果能开发出来，可卡因依赖的生物标志物将对制药行业和公共卫生都具有巨大价值。
