Cargando…

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

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 promi...

Descripción completa

Detalles Bibliográficos
Autores principales: Fang, J, Cai, C, Wang, Q, Lin, P, Zhao, Z, Cheng, F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356618/
https://www.ncbi.nlm.nih.gov/pubmed/28294568
http://dx.doi.org/10.1002/psp4.12172
_version_ 1782515875056713728
author Fang, J
Cai, C
Wang, Q
Lin, P
Zhao, Z
Cheng, F
author_facet Fang, J
Cai, C
Wang, Q
Lin, P
Zhao, Z
Cheng, F
author_sort Fang, J
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5356618
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-53566182017-03-22 Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes Fang, J Cai, C Wang, Q Lin, P Zhao, Z Cheng, F CPT Pharmacometrics Syst Pharmacol Original Articles 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. John Wiley and Sons Inc. 2017-03-14 2017-03 /pmc/articles/PMC5356618/ /pubmed/28294568 http://dx.doi.org/10.1002/psp4.12172 Text en © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Fang, J
Cai, C
Wang, Q
Lin, P
Zhao, Z
Cheng, F
Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes
title Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes
title_full Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes
title_fullStr Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes
title_full_unstemmed Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes
title_short Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes
title_sort systems pharmacology‐based discovery of natural products for precision oncology through targeting cancer mutated genes
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356618/
https://www.ncbi.nlm.nih.gov/pubmed/28294568
http://dx.doi.org/10.1002/psp4.12172
work_keys_str_mv AT fangj systemspharmacologybaseddiscoveryofnaturalproductsforprecisiononcologythroughtargetingcancermutatedgenes
AT caic systemspharmacologybaseddiscoveryofnaturalproductsforprecisiononcologythroughtargetingcancermutatedgenes
AT wangq systemspharmacologybaseddiscoveryofnaturalproductsforprecisiononcologythroughtargetingcancermutatedgenes
AT linp systemspharmacologybaseddiscoveryofnaturalproductsforprecisiononcologythroughtargetingcancermutatedgenes
AT zhaoz systemspharmacologybaseddiscoveryofnaturalproductsforprecisiononcologythroughtargetingcancermutatedgenes
AT chengf systemspharmacologybaseddiscoveryofnaturalproductsforprecisiononcologythroughtargetingcancermutatedgenes