Systems biology approaches for advancing the discovery of effective drug combinations Rajarshi Guha

Karen A. Ryall, Aik-Choon Tan

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Complex diseases like cancer are regulated by large, interconnected networks with many pathways affecting cell proliferation, invasion, and drug resistance. However, current cancer therapy predominantly relies on the reductionist approach of one gene-one disease. Combinations of drugs may overcome drug resistance by limiting mutations and induction of escape pathways, but given the enormous number of possible drug combinations, strategies to reduce the search space and prioritize experiments are needed. In this review, we focus on the use of computational modeling, bioinformatics and high-throughput experimental methods for discovery of drug combinations. We highlight cutting-edge systems approaches, including large-scale modeling of cell signaling networks, network motif analysis, statistical association-based models, identifying correlations in gene signatures, functional genomics, and high-throughput combination screens. We also present a list of publicly available data and resources to aid in discovery of drug combinations. Integration of these systems approaches will enable faster discovery and translation of clinically relevant drug combinations.

Original languageEnglish
Article number7
JournalJournal of Cheminformatics
Volume7
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Drug Combinations
biology
drugs
Genes
Throughput
Cell signaling
drug
Cell proliferation
Bioinformatics
Electric network analysis
genes
cancer
Disease
Pharmaceutical Preparations
Experiments
network analysis
mutations
Systems Biology
invasion
induction

Keywords

  • Cancer
  • Computational modeling
  • Drug combinations
  • Drug discovery
  • Systems biology

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Computer Science Applications
  • Library and Information Sciences

Cite this

Systems biology approaches for advancing the discovery of effective drug combinations Rajarshi Guha. / Ryall, Karen A.; Tan, Aik-Choon.

In: Journal of Cheminformatics, Vol. 7, No. 1, 7, 2015.

Research output: Contribution to journalArticle

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