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

  • Alok Jaiswal
  • Bhagwan Yadav
  • Krister Wennerberg
  • Tero AittokallioEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1888)


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.

Key words

Precision oncology Drug sensitivity testing Drug polypharmacology Drug–target interactions Target addictions Target deconvolution Drug combinations 



This work was supported by the Academy of Finland (grants 272437, 269862, 279163, 292611, 295504, 310507); the Cancer Society of Finland (TA, KW); the Integrative Life Science Doctoral Program at the University of Helsinki (AJ).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alok Jaiswal
    • 1
  • Bhagwan Yadav
    • 2
  • Krister Wennerberg
    • 1
  • Tero Aittokallio
    • 1
    • 3
    Email author
  1. 1.Institute for Molecular Medicine Finland (FIMM)University of HelsinkiHelsinkiFinland
  2. 2.Hematology Research Unit Helsinki (HRUH)University of HelsinkiHelsinkiFinland
  3. 3.Department of Mathematics and StatisticsUniversity of TurkuTurkuFinland

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