Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Author
Date
2019-06-17
Department
Department of Computer Science
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Mcode
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Language
en
Pages
17
1-17
Series
Nature Communications, Volume 10, issue 1
Abstract
The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
Description
| openaire: EC/H2020/668858/EU//PrECISE
Keywords
ANDROGEN RECEPTOR, BREAST-CANCER, GENE, CELL, INHIBITION, RESISTANCE, PATHWAY, MUTATIONS, LANDSCAPE, RESOURCE
Other note
DOI
10.1038/s41467-019-09799-2
Citation
Kaski, S, Marttinen, P & AstraZeneca-Sanger Drug Combination DREAM Consortium 2019, ' Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen ', Nature Communications, vol. 10, no. 1, 2674, pp. 1-17 . https://doi.org/10.1038/s41467-019-09799-2
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https://urn.fi/URN:NBN:fi:aalto-201907304463
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[article-cris] Perustieteiden korkeakoulu / SCI