AUTHOR=Chamberlin Steven R. , Blucher Aurora , Wu Guanming , Shinto Lynne , Choonoo Gabrielle , Kulesz-Martin Molly , McWeeney Shannon 

TITLE=Natural Product Target Network Reveals Potential for Cancer Combination Therapies

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00557

DOI=10.3389/fphar.2019.00557

ISSN=1663-9812

ABSTRACT=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 conducted a thorough survey for natural products using pathway and network-based approaches. When considering pathways from the Reactome database targeted only by natural products, at all levels of evidence, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved antineoplastic drugs collected in the Cancer Targetome, a collective drug/target interaction resource for these drugs. 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. We examined the distribution of cancer driver genes across pathways and found 24 pathways enriched for cancer drivers that had no cancer drug interactions (when requiring a binding affinity threshold of < 100 nM), but did have 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.