دورية أكاديمية
Predicting tumor response to drugs based on gene-expression biomarkers of sensitivity learned from cancer cell lines
| العنوان: | Predicting tumor response to drugs based on gene-expression biomarkers of sensitivity learned from cancer cell lines |
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| المؤلفون: | Yuanyuan Li, David M. Umbach, Juno M. Krahn, Igor Shats, Xiaoling Li, Leping Li |
| المصدر: | BMC Genomics, Vol 22, Iss 1, Pp 1-18 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biotechnology LCC:Genetics |
| مصطلحات موضوعية: | Drug sensitivity, RNA-seq, Cancer cell line, GDSC, GA/KNN, TCGA, Biotechnology, TP248.13-248.65, Genetics, QH426-470 |
| الوصف: | Abstract Background Human cancer cell line profiling and drug sensitivity studies provide valuable information about the therapeutic potential of drugs and their possible mechanisms of action. The goal of those studies is to translate the findings from in vitro studies of cancer cell lines into in vivo therapeutic relevance and, eventually, patients’ care. Tremendous progress has been made. Results In this work, we built predictive models for 453 drugs using data on gene expression and drug sensitivity (IC50) from cancer cell lines. We identified many known drug-gene interactions and uncovered several potentially novel drug-gene associations. Importantly, we further applied these predictive models to ~ 17,000 bulk RNA-seq samples from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to predict drug sensitivity for both normal and tumor tissues. We created a web site for users to visualize and download our predicted data ( https://manticore.niehs.nih.gov/cancerRxTissueTest ). Using trametinib as an example, we showed that our approach can faithfully recapitulate the known tumor specificity of the drug. Conclusions We demonstrated that our approach can predict drugs that 1) are tumor-type specific; 2) elicit higher sensitivity from tumor compared to corresponding normal tissue; 3) elicit differential sensitivity across breast cancer subtypes. If validated, our prediction could have relevance for preclinical drug testing and in phase I clinical design. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1471-2164 |
| العلاقة: | https://doaj.org/toc/1471-2164Test |
| DOI: | 10.1186/s12864-021-07581-7 |
| الوصول الحر: | https://doaj.org/article/4b1de6683af848de92c5bf39c5ce389fTest |
| رقم الانضمام: | edsdoj.4b1de6683af848de92c5bf39c5ce389f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14712164 |
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| DOI: | 10.1186/s12864-021-07581-7 |