Next Article in Journal
The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study
Previous Article in Journal
A Metabolomics Approach Uncovers Differences between Traditional and Commercial Dairy Products in Buryatia (Russian Federation)
Open AccessArticle

Facilitating Anti-Cancer Combinatorial Drug Discovery by Targeting Epistatic Disease Genes

1
Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China
2
School of Life Sciences, Shandong University of Technology; No. 12 Zhangzhou Road, Zibo 255049, China
3
Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2018, 23(4), 736; https://doi.org/10.3390/molecules23040736
Received: 25 January 2018 / Revised: 15 March 2018 / Accepted: 20 March 2018 / Published: 23 March 2018
Due to synergistic effects, combinatorial drugs are widely used for treating complex diseases. However, combining drugs and making them synergetic remains a challenge. Genetic disease genes are considered a promising source of drug targets with important implications for navigating the drug space. Most diseases are not caused by a single pathogenic factor, but by multiple disease genes, in particular, interacting disease genes. Thus, it is reasonable to consider that targeting epistatic disease genes may enhance the therapeutic effects of combinatorial drugs. In this study, synthetic lethality gene pairs of tumors, similar to epistatic disease genes, were first targeted by combinatorial drugs, resulting in the enrichment of the combinatorial drugs with cancer treatment, which verified our hypothesis. Then, conventional epistasis detection software was used to identify epistatic disease genes from the genome wide association studies (GWAS) dataset. Furthermore, combinatorial drugs were predicted by targeting these epistatic disease genes, and five combinations were proven to have synergistic anti-cancer effects on MCF-7 cells through cell cytotoxicity assay. Combined with the three-dimensional (3D) genome-based method, the epistatic disease genes were filtered and were more closely related to disease. By targeting the filtered gene pairs, the efficiency of combinatorial drug discovery has been further improved. View Full-Text
Keywords: combinatorial drug; drug target; GWAS; epistasis; 3D genome combinatorial drug; drug target; GWAS; epistasis; 3D genome
Show Figures

Figure 1

MDPI and ACS Style

Quan, Y.; Liu, M.-Y.; Liu, Y.-M.; Zhu, L.-D.; Wu, Y.-S.; Luo, Z.-H.; Zhang, X.-Z.; Xu, S.-Z.; Yang, Q.-Y.; Zhang, H.-Y. Facilitating Anti-Cancer Combinatorial Drug Discovery by Targeting Epistatic Disease Genes. Molecules 2018, 23, 736.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop