Integrated Analysis of Drug Sensitivity and Selectivity to Predict Synergistic Drug Combinations and Target Coaddictions in Cancer.

Integrated Analysis of Drug Sensitivity and Selectivity to Predict Synergistic Drug Combinations and Target Coaddictions in Cancer. Methods Mol Biol. 2019;1888:205-217 Authors: Jaiswal A, Yadav B, Wennerberg K, Aittokallio T Abstract High-throughput drug sensitivity testing provides a powerful phenotypic profiling approach to identify effective drug candidates for individual cell lines or patient-derived samples. Here, we describe an experimental-computational pipeline, named target addiction scoring (TAS), which mathematically transforms the drug response profiles into target addiction signatures, and thereby provides a ranking of potential therapeutic targets according to their functional importance in a particular cancer sample. The TAS pipeline makes use of drug polypharmacology to integrate the drug sensitivity and selectivity profiles through systems-wide interconnection networks between drugs and their targets, including both primary protein targets as well as secondary off-targets. We show how the TAS pipeline enables one to identify not only single-target addictions but also combinatorial coaddictions among targets that often underlie synergistic drug combinations. PMID: 30519949 [PubMed - in process]
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research