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      Computational models for predicting drug responses in cancer research

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          Abstract

          The computational prediction of drug responses based on the analysis of multiple types of genome-wide molecular data is vital for accomplishing the promise of precision medicine in oncology. This will benefit cancer patients by matching their tumor characteristics to the most effective therapy available. As larger and more diverse layers of patient-related data become available, further demands for new bioinformatics approaches and expertise will arise. This article reviews key strategies, resources and techniques for the prediction of drug sensitivity in cell lines and patient-derived samples. It discusses major advances and challenges associated with the different model development steps. This review highlights major trends in this area, and will assist researchers in the assessment of recent progress and in the selection of approaches to emerging applications in oncology.

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          Most cited references49

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          pRRophetic: An R Package for Prediction of Clinical Chemotherapeutic Response from Tumor Gene Expression Levels

          We recently described a methodology that reliably predicted chemotherapeutic response in multiple independent clinical trials. The method worked by building statistical models from gene expression and drug sensitivity data in a very large panel of cancer cell lines, then applying these models to gene expression data from primary tumor biopsies. Here, to facilitate the development and adoption of this methodology we have created an R package called pRRophetic. This also extends the previously described pipeline, allowing prediction of clinical drug response for many cancer drugs in a user-friendly R environment. We have developed several other important use cases; as an example, we have shown that prediction of bortezomib sensitivity in multiple myeloma may be improved by training models on a large set of neoplastic hematological cell lines. We have also shown that the package facilitates model development and prediction using several different classes of data.
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            The NCI60 human tumour cell line anticancer drug screen.

            The US National Cancer Institute (NCI) 60 human tumour cell line anticancer drug screen (NCI60) was developed in the late 1980s as an in vitro drug-discovery tool intended to supplant the use of transplantable animal tumours in anticancer drug screening. This screening model was rapidly recognized as a rich source of information about the mechanisms of growth inhibition and tumour-cell kill. Recently, its role has changed to that of a service screen supporting the cancer research community. Here I review the development, use and productivity of the screen, highlighting several outcomes that have contributed to advances in cancer chemotherapy.
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              Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines

              We demonstrate a method for the prediction of chemotherapeutic response in patients using only before-treatment baseline tumor gene expression data. First, we fitted models for whole-genome gene expression against drug sensitivity in a large panel of cell lines, using a method that allows every gene to influence the prediction. Following data homogenization and filtering, these models were applied to baseline expression levels from primary tumor biopsies, yielding an in vivo drug sensitivity prediction. We validated this approach in three independent clinical trial datasets, and obtained predictions equally good, or better than, gene signatures derived directly from clinical data.
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                Author and article information

                Journal
                Brief Bioinform
                Brief. Bioinformatics
                bib
                Briefings in Bioinformatics
                Oxford University Press
                1467-5463
                1477-4054
                September 2017
                21 July 2016
                21 July 2016
                : 18
                : 5
                : 820-829
                Affiliations
                NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg
                Author notes
                Corresponding author: Francisco Azuaje, NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg L-1526, Luxembourg. Tel.: +352-26970875; Fax: +352-26970396; E-mail: Francisco.Azuaje@ 123456lih.lu
                Article
                bbw065
                10.1093/bib/bbw065
                5862310
                27444372
                17aa587e-9c96-404b-b93e-c551910a8bed
                © The Author 2016. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 18 March 2016
                : 7 June 2016
                Page count
                Pages: 10
                Categories
                Papers

                Bioinformatics & Computational biology
                drug sensitivity,computational prediction models,cancer,translational bioinformatics,precision medicine

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