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CPT Pharmacometrics Syst Pharmacol. 2017 Mar;6(3):177-187. doi: 10.1002/psp4.12172. Epub 2017 Mar 14.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

Author information

1
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China.
2
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, P.R. China.
3
Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
4
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.
5
Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
6
Center for Complex Networks Research, Northeastern University, Boston, Massachusetts, USA.

Abstract

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products.

PMID:
28294568
PMCID:
PMC5356618
DOI:
10.1002/psp4.12172
[Indexed for MEDLINE]
Free PMC Article

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