Poornima Paramasivan, Kumar Jothi Dinesh, Zhao Qiaoli, Blunder Martina, Efferth Thomas
School of Chemistry, Bangor University, Bangor, Gwynedd LL57 2DG, United Kingdom.
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, United Kingdom.
Pharmacol Res. 2016 Sep;111:290-302. doi: 10.1016/j.phrs.2016.06.018. Epub 2016 Jun 18.
Despite massive investments in drug research and development, the significant decline in the number of new drugs approved or translated to clinical use raises the question, whether single targeted drug discovery is the right approach. To combat complex systemic diseases that harbour robust biological networks such as cancer, single target intervention is proved to be ineffective. In such cases, network pharmacology approaches are highly useful, because they differ from conventional drug discovery by addressing the ability of drugs to target numerous proteins or networks involved in a disease. Pleiotropic natural products are one of the promising strategies due to their multi-targeting and due to lower side effects. In this review, we discuss the application of network pharmacology for cancer drug discovery. We provide an overview of the current state of knowledge on network pharmacology, focus on different technical approaches and implications for cancer therapy (e.g. polypharmacology and synthetic lethality), and illustrate the therapeutic potential with selected examples green tea polyphenolics, Eleutherococcus senticosus, Rhodiola rosea, and Schisandra chinensis). Finally, we present future perspectives on their plausible applications for diagnosis and therapy of cancer.
尽管在药物研发方面投入巨大，但获批或转化为临床应用的新药数量显著下降，这引发了一个问题：单一靶点药物研发是否是正确的方法。事实证明，对于像癌症这样拥有强大生物网络的复杂系统性疾病，单一靶点干预是无效的。在这种情况下，网络药理学方法非常有用，因为它们与传统药物研发不同，能够研究药物针对疾病中多种蛋白质或网络的靶向能力。多效性天然产物因其多靶点作用和较低的副作用，是一种很有前景的策略。在这篇综述中，我们讨论了网络药理学在癌症药物研发中的应用。我们概述了网络药理学的当前知识状态，重点介绍了不同的技术方法及其对癌症治疗的影响（如多药理学和合成致死性），并通过选定的例子（绿茶多酚、刺五加、红景天和五味子）来说明其治疗潜力。最后，我们阐述了它们在癌症诊断和治疗方面可能应用的未来前景。
