A major challenge in cancer treatment is predicting clinical response to anti-cancer drugs on a personalized basis. Using a pharmacogenomics database of 1,001 cancer cell lines, we trained deep neural networks for prediction of drug response and assessed their performance on multiple clinical cohorts. We demonstrate that deep neural networks outperform the current state in machine learning frameworks. We provide a proof of concept for the use of deep neural network-based frameworks to aid precision oncology strategies.

1st Department of Propaedeutic Internal Medicine Medical School Laikon Hospital National and Kapodistrian University of Athens 75 Mikras Asias Str Athens 11527 Greece; Center for New Biotechnologies and Precision Medicine Medical School National and Kapodistrian University of Athens 75 Mikras Asias Str Athens 11527 Greece

Applied Bioinformatics Laboratories NYU School of Medicine New York NY 10016 USA

Biomedical Research Foundation of the Academy of Athens 4 Soranou Ephessiou Str Athens 11527 Greece

Biomedical Research Foundation of the Academy of Athens 4 Soranou Ephessiou Str Athens 11527 Greece; Molecular Carcinogenesis Group Department of Histology and Embryology School of Medicine National and Kapodistrian University of Athens 75 Mikras Asias Str Athens 11527 Greece

Biomedical Research Foundation of the Academy of Athens 4 Soranou Ephessiou Str Athens 11527 Greece; Molecular Carcinogenesis Group Department of Histology and Embryology School of Medicine National and Kapodistrian University of Athens 75 Mikras Asias Str Athens 11527 Greece; Division of Cancer Sciences Faculty of Biology Medicine and Health Manchester Academic Health Science Centre Manchester Cancer Research Centre NIHR Manchester Biomedical Research Centre University of Manchester Manchester M20 4GJ UK; 1st Department of Propaedeutic Internal Medicine Medical School Laikon Hospital National and Kapodistrian University of Athens 75 Mikras Asias Str Athens 11527 Greece

Department of Applied Sciences Northumbria University Newcastle upon Tyne NE1 8ST UK; Department of Electron Microscopy and Molecular Pathology Cyprus Institute of Neurology and Genetics Nicosia 2371 Cyprus

Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd Houston TX 77030 USA

Department of Pathology NYU School of Medicine New York NY 10016 USA; Laura and Isaac Perlmutter Cancer Center NYU School of Medicine New York NY 10016 USA

Department of Pathology NYU School of Medicine New York NY 10016 USA; Laura and Isaac Perlmutter Cancer Center NYU School of Medicine New York NY 10016 USA; Applied Bioinformatics Laboratories NYU School of Medicine New York NY 10016 USA

Division of Cancer Sciences Faculty of Biology Medicine and Health Manchester Academic Health Science Centre Manchester Cancer Research Centre NIHR Manchester Biomedical Research Centre University of Manchester Manchester M20 4GJ UK

Division of Molecular and Clinical Medicine Ninewells Hospital and School of Medicine University of Dundee Dundee DD1 9SY UK

Genome Integrity Unit Danish Cancer Society Research Centre Strandboulevarden 49 Copenhagen 2100 Denmark; Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Hněvotínská Olomouc 1333 5 779 00 Czech Republic; Science for Life Laboratory Division of Genome Biology Department of Medical Biochemistry and Biophysics Karolinska Institute Stockholm SE 171 77 Sweden

Medical Research Council Cancer Unit Hutchison Medical Research Council Research Centre University of Cambridge Cambridge CB2 0XZ UK

Molecular Carcinogenesis Group Department of Histology and Embryology School of Medicine National and Kapodistrian University of Athens 75 Mikras Asias Str Athens 11527 Greece

Sanford 1 Weill Department of Medicine Sandra and Edward Meyer Cancer Center Weill Cornell Medicine New York NY 10021 USA

School of Mechanical Engineering National Technical University of Athens Zografou 15780 Greece

Sheikh Khalifa Bin Zayed al Nahyan Institute for Personalized Cancer Therapy The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd Houston TX 77030 USA

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