Liu Jun, Wang Zhong
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Acta Pharmacol Sin. 2015 Jun;36(6):680-8. doi: 10.1038/aps.2014.125. Epub 2015 Apr 13.
In line with the complexity of disease networks, diverse combination therapies have been demonstrated potential in the treatment of different patients with complex diseases in a personal combination profile. However, the identification of rational, compatible and effective drug combinations remains an ongoing challenge. Based on a holistic theory integrated with reductionism, Fangjiomics systematically develops multiple modes of array-designed combination therapies. We define diverse "magic shotgun" vertical, horizontal, focusing, siege and dynamic arrays according to different spatiotemporal distributions of hits on targets, pathways and networks. Through these multiple adaptive modes for treating complex diseases, Fangjiomics may help to identify rational drug combinations with synergistic or additive efficacy but reduced adverse side effects that reverse complex diseases by reconstructing or rewiring multiple targets, pathways and networks. Such a novel paradigm for combination therapies may allow us to achieve more precise treatments by developing phenotype-driven quantitative multi-scale modeling for rational drug combinations.
鉴于疾病网络的复杂性，多种联合疗法已被证明在根据个人联合治疗方案治疗不同复杂疾病患者方面具有潜力。然而，确定合理、兼容且有效的药物组合仍然是一项持续的挑战。基于与还原论相结合的整体理论，方剂组学系统地开发了多种阵列设计的联合治疗模式。我们根据靶点、通路和网络上命中的不同时空分布，定义了多种“神奇散弹枪”垂直、水平、聚焦、围攻和动态阵列。通过这些治疗复杂疾病的多种自适应模式，方剂组学可能有助于识别具有协同或相加疗效但副作用减少的合理药物组合，通过重建或重新连接多个靶点、通路和网络来逆转复杂疾病。这种联合治疗的新范式可能使我们通过开发用于合理药物组合的表型驱动定量多尺度模型来实现更精确的治疗。
