Systems biology approaches for advancing the discovery of effective drug combinations

By Karen A. Ryall, Aik Choon Tan. 2015

143 citations recorded by the source corpus.

AbstractComplex 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. Graphical abstractSpectrum of Systems Biology Approaches for Drug Combinations.

Subfields: Computational Theory and Mathematics, Molecular Biology

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Citations in the corpus

Modeling polypharmacy side effects with graph convolutional networks (2018, background): “In vitro experiments and clinical trials can be performed to identify drug-drug interactions (Li et al., 2015; Ryall and Tan, 2015), but systematic combinatorial screening of drug-drug interaction candidates remains challenging and expensive (Bansal et al.”
Machine Learning for Integrating Data in Biology and Medicine: Principles, Practice, and Opportunities (2018, methodology): “To address this combinatorial explosion of candidate drug combinations, computational methods were developed to identify drug pairs that potentially interact [282].”
Synergy Maps: exploring compound combinations using network-based visualization (2015, background): “Two recent reviews are available on the topic [9, 10].”