Fangjiomics: In Search of Effective and Safe Combination Therapies

Abstract

Millennia-old Chinese medicine treats disease with many combination therapies involving ingredients used in clinic practice. Fangjiomics is the science of identifying and designing effective mixtures of bioactive agents and elucidating their modes of action beyond those of Chinese patent medicines. Omics profiling and quantitative optimal modeling have been used to associate the various responses with biological pathways related to disease phenotype. Fangjiomics seeks to study myriad compatible combinations that may act through multiple targets, modes of action, and biological pathways balancing on off-target and on-target effects. This approach may lead to the discovery of controllable array-designed therapies to combine less potent elements that are more effective collectively but have fewer adverse side effects than does any element singly.

Diverse array-designed modes of combination therapies in Fangjiomics

“…Fangjiomics is the large-scale study of combination therapies, including their combination modes, the drug-drug interactions involved in the combinations, the mechanism of the pharmacological actions of the combinations, etc. As discussed in our previous paper, the philosophy of Fangjiomics is distinct from conventional approaches in the aspects of theory, hypothesis, objective, and subject pharmacology, as well as in the process [24] . This therapeutic strategy targets multi-scale biological network levels [25] , including the molecular, cellular, tissue, and organ levels, which are related to clinical outcomes as profiled effects based on a holistic theory integrated with reductionism.…”

“…Thus far, more than tens of thousands of Fangjis have been recorded in different books [24] . Fangjiomics is the large-scale study of combination therapies, including their combination modes, the drug-drug interactions involved in the combinations, the mechanism of the pharmacological actions of the combinations, etc.…”

“…Fangjiomics is an emerging science for the design, production, and evaluation of combination therapy rationally selected from diverse agents in the holistic treatment of complex diseases [24] . In contrast to traditional "omics" techniques focusing on a certain level of cell, tissue, or organ, this holistic therapeutic strategy uses rational drug combinations with higher efficacy but fewer adverse effects in a controlled array design by integrating diverse scale omics data on gene, protein, and metabolic interactions.…”

Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2 diabetes in mice by a Fangjiomics approach

“…Fangjiomics is the science of designing effective mixtures of Fangjis and elucidating their modes of action often by combining omics technologies [11] , and network pharmacology offers a network perspective to understand the relationships between drugs and targets. By integrating system-level omics data (eg, transcriptome expression data) with network-based analyses, a new avenue has emerged to help explain the complex therapeutic mechanisms of Fangji.…”

Phenotype-dependent alteration of pathways and networks reveals a pure synergistic mechanism for compounds treating mouse cerebral ischemia

“…A great deal of emphasis has been placed on combination therapy for cerebral ischemia, which is thought to be more effective and has fewer adverse effects than single therapies [1,2] . Our understanding of the synergistic properties of many current or possible combination therapies has implications for improving therapeutic efficacy and safety [3] .…”