Natural Product Target Network Reveals Potential for Cancer Combination Therapies

A body of research demonstrates examples of and synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence...

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Vydáno v:Frontiers in pharmacology Ročník 10; s. 557
Hlavní autoři: Chamberlin, Steven R., Blucher, Aurora, Wu, Guanming, Shinto, Lynne, Choonoo, Gabrielle, Kulesz-Martin, Molly, McWeeney, Shannon
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 31.05.2019
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ISSN:1663-9812, 1663-9812
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Abstract A body of research demonstrates examples of and synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products.
AbstractList A body of research demonstrates examples of in vitro and in vivo synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products.A body of research demonstrates examples of in vitro and in vivo synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products.
A body of research demonstrates examples of in vitro and in vivo synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products.
A body of research demonstrates examples of and synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products.
Author Kulesz-Martin, Molly
Chamberlin, Steven R.
Choonoo, Gabrielle
Wu, Guanming
Shinto, Lynne
McWeeney, Shannon
Blucher, Aurora
AuthorAffiliation 1 Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology , Portland, OR , United States
3 Oregon Clinical and Translational Research Institute , Portland, OR , United States
4 Department of Neurology, Oregon Health and Science University , Portland, OR , United States
5 Departments of Dermatology and Cell, Developmental and Cancer Biology, Oregon Health and Sciences University , Portland, OR , United States
2 OHSU Knight Cancer Institute , Portland, OR , United States
AuthorAffiliation_xml – name: 5 Departments of Dermatology and Cell, Developmental and Cancer Biology, Oregon Health and Sciences University , Portland, OR , United States
– name: 2 OHSU Knight Cancer Institute , Portland, OR , United States
– name: 3 Oregon Clinical and Translational Research Institute , Portland, OR , United States
– name: 1 Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology , Portland, OR , United States
– name: 4 Department of Neurology, Oregon Health and Science University , Portland, OR , United States
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/31214023$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright Copyright © 2019 Chamberlin, Blucher, Wu, Shinto, Choonoo, Kulesz-Martin and McWeeney. 2019 Chamberlin, Blucher, Wu, Shinto, Choonoo, Kulesz-Martin and McWeeney
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Keywords cancer
synergy
therapeutic targets
antineoplastic drug
natural product
Language English
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This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology
Edited by: Brion William Murray, Pfizer, United States
Reviewed by: Marco Falasca, Curtin University, Australia; Marcello Locatelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
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Snippet A body of research demonstrates examples of and synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological...
A body of research demonstrates examples of in vitro and in vivo synergy between natural products and anti-neoplastic drugs for some cancers. However, the...
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SubjectTerms antineoplastic drug
cancer
natural product
Pharmacology
synergy
therapeutic targets
Title Natural Product Target Network Reveals Potential for Cancer Combination Therapies
URI https://www.ncbi.nlm.nih.gov/pubmed/31214023
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