Diverse array-designed modes of combination therapies in Fangjiomics

Abstract

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.

Yangxin Tongmai Formula ameliorates impaired glucose tolerance in children with Graves' disease through upregulation of the insulin receptor levels

“…GD2 group had normal glucose tolerance. believe that this is the ultimate goal of Fangjiomics [8][9][10][11] , which takes advantage of TCM to promote systematic reactions in the human body to actually cure the disease and not only treat the symptoms. In fact, other groups have followed the guidance of Fangjiomics to explore the molecular actions of the Traditional Chinese Herbal Formula for the treatment of diabetes [13] .…”

“…Although the ultimate goal of both TCM and Western medicine is to cure diseases, there are fundamental and conceptual differences between TCM and Western medicine. TCM treats the human body and disease as an integrated system, and the crosstalk among different organs and the interplay of various symptoms are all taken into consideration when a TCM doctor diagnoses patients [8][9][10][11] . In TCM terminology, diabetes is called Xiao-ke, which is caused by an improper diet, emotional disturbances and, most critically, Yin deficiency, in which patients exhibit fatigue, weakness and tiredness.…”

New omic and network paradigms for deep understanding of therapeutic mechanisms for Fangji of traditional Chinese medicine

“…Combination therapy with multi-drug regimen as an integrated intervention of several pharmacological compounds that interact with multiple targets, rather than monotherapy using a single compound that targets at a single molecule, is a common strategy for combating complex disease in both Western and traditional Chinese medicine (TCM) [1][2][3] . But each is based on different mechanistic principles.…”

“…The ingredients in a Fangji were thus composed according to the quaternity of Jun (monarch), which targets at the major etiological mechanisms, Chen (minister), which targets at the secondary etiological mechanisms, Zuo (assistant or associate), which targets at the associated factors to facilitate the therapeutic effects or reduce the adverse effects, and Shi (guide), which guides and orchestrates the targets [4] . Therefore, TCM Fangji combination therapy has embodied many principles of modern systems biology and omic theories [2,3] . The therapeutic effects of TCM Fangji rely on the integrated whole function through compatibility of the drugs in the multi-drug regimen of Fangji [2] .…”

Fangjiomics: revealing adaptive omics pharmacological mechanisms of the myriad combination therapies to achieve personalized medicine

“…Wang et al summarized the recent investigations on the anticancer activities and possible molecular targets of the Compound Kusen Injection, and then hypothesized that altering gene regulation in several pathways including Wnt signaling pathway might be involved in the underlying mechanisms [9] . To summarize the targets distribution of Fangjis, Liu and Wang defined multiple modes of array-designed combination therapies of Fangjiomics, such as "magic shotguns", vertical, horizontal, focusing, siege and dynamic arrays according to hits on targets, pathways or networks [10] . Also included in this Special Issue are six original research articles that delineate the systematic and network approaches of Fangjiomics on several popular Zheng-hous or Fangjis, which are commonly used in TCM practice.…”