6533b85efe1ef96bd12bfe19

RESEARCH PRODUCT

Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature

Jothi Dinesh KumarParamasivan PoornimaMartina BlunderQiaoli ZhaoThomas Efferth

subject

EpigenomicsProteomics0301 basic medicineDrugmedia_common.quotation_subjectSystems biologyGene regulatory networkSynthetic lethalityDiseaseComputational biologyBiologyPharmacology03 medical and health sciencesNeoplasmsDrug DiscoveryBiomarkers TumormedicineAnimalsHumansMetabolomicsGene Regulatory NetworksMolecular Targeted TherapyProtein Interaction Mapsmedia_commonPharmacologyPlants MedicinalDrug discoveryGene Expression ProfilingSystems BiologyCancermedicine.diseaseAntineoplastic Agents PhytogenicGene Expression Regulation Neoplastic030104 developmental biologyBiological networkPhytotherapySignal Transduction

description

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.

https://doi.org/10.1016/j.phrs.2016.06.018