@article{2c3f63c0c16a47f6a82ae01b3cf9bfc2,
title = "Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen",
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{\textquoteright}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.",
keywords = "ANDROGEN RECEPTOR, BREAST-CANCER, GENE, CELL, INHIBITION, RESISTANCE, PATHWAY, MUTATIONS, LANDSCAPE, RESOURCE",
author = "Menden, {Michael P.} and Dennis Wang and Mason, {Mike J.} and Bence Szalai and Bulusu, {Krishna C.} and Yuanfang Guan and Thomas Yu and Jaewoo Kang and Minji Jeon and Russ Wolfinger and Tin Nguyen and Mikhail Zaslavskiy and Jordi Abante and Abecassis, {Barbara Schmitz} and Nanne Aben and Delasa Aghamirzaie and Tero Aittokallio and Akhtari, {Farida S.} and Bissan Al-lazikani and Tanvir Alam and Amin Allam and Chad Allen and {de Almeida}, {Mariana Pelicano} and Doaa Altarawy and Vinicius Alves and Alicia Amadoz and Benedict Anchang and Antolin, {Albert A.} and Ash, {Jeremy R.} and Aznar, {Victoria Romeo} and Wail Ba-alawi and Moeen Bagheri and Vladimir Bajic and Gordon Ball and Ballester, {Pedro J.} and Delora Baptista and Christopher Bare and Mathilde Bateson and Andreas Bender and Denis Bertrand and Bhagya Wijayawardena and Boroevich, {Keith A.} and Evert Bosdriesz and Mehmet Gonen and Samuel Kaski and Khan, {Suleiman Ali} and Hiroshi Mamitsuka and Pekka Marttinen and Xin Wang and Alexey Zakharov and {AstraZeneca-Sanger Drug Combination DREAM Consortium}",
note = "| openaire: EC/H2020/668858/EU//PrECISE ",
year = "2019",
month = jun,
day = "17",
doi = "10.1038/s41467-019-09799-2",
language = "English",
volume = "10",
pages = "1--17",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Portfolio",
number = "1",
}