title: Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature.
abstract: 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.
authors.affiliation: School of Chemistry, Bangor University, Bangor, Gwynedd LL57 2DG, United Kingdom.
authors.forename: Paramasivan
authors.initials: P
authors.lastname: Poornima
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, United Kingdom.
authors.forename: Jothi Dinesh
authors.initials: JD
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden and Brain Institute, Federal University of Rio Grande do Norte, UFRN, Natal, Brazil.
authors.forename: Martina
authors.initials: M
authors.lastname: Blunder
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany. Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D055808:Drug Discovery / Q000379:methods*; D057890:Epigenomics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D055432:Metabolomics; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010946:Plants, Medicinal; D060066:Protein Interaction Maps; D040901:Proteomics; D015398:Signal Transduction / Q000187:drug effects; D049490:Systems Biology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor
keywords: Eleutherococcus senticosus; Genomics; Green tea polyphenolics; Lithospermum erythrorhizon; Metabolomics; Polypharmacology; Proteomics; Rhodiola rosea; Schisandra chinensis; Synthetic lethality; Systems biology; Transcriptomics