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      Big Data Approaches for Modeling Response and Resistance to Cancer Drugs

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          Abstract

          Despite significant progress in cancer research, current standard-of-care drugs fail to cure many types of cancers. Hence, there is an urgent need to identify better predictive biomarkers and treatment regimes. Conventionally, insights from hypothesis-driven studies are the primary force for cancer biology and therapeutic discoveries. Recently, the rapid growth of big data resources, catalyzed by breakthroughs in high-throughput technologies, has resulted in a paradigm shift in cancer therapeutic research. The combination of computational methods and genomics data has led to several successful clinical applications. In this review, we focus on recent advances in data-driven methods to model anticancer drug efficacy, and we present the challenges and opportunities for data science in cancer therapeutic research.

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          A tutorial on support vector regression

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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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              Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

              The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
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                Author and article information

                Journal
                101714020
                48523
                Annu Rev Biomed Data Sci
                Annu Rev Biomed Data Sci
                Annual review of biomedical data science
                2574-3414
                18 June 2019
                25 April 2018
                July 2018
                24 July 2019
                : 1
                : 1-27
                Affiliations
                [1 ]Dana–Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02215, USA
                [2 ]Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
                Article
                PMC6655478 PMC6655478 6655478 nihpa1028113
                10.1146/annurev-biodatasci-080917-013350
                6655478
                31342013
                dd223ddf-5192-422d-8df5-449be163007b
                History
                Categories
                Article

                toxicity,combination therapy,response biomarker,drug resistance,immunotherapy,precision medicine,big data

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