دورية أكاديمية
Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset.
| العنوان: | Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset. |
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| المؤلفون: | Seashore-Ludlow B; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Rees MG; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Cheah JH; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Cokol M; Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey., Price EV; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Coletti ME; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Jones V; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Bodycombe NE; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Soule CK; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Gould J; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Alexander B; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Li A; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Montgomery P; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Wawer MJ; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Kuru N; Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey., Kotz JD; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Hon CS; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Munoz B; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Liefeld T; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Dančík V; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Bittker JA; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Palmer M; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts., Bradner JE; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts. Cancer Biology and Medical Oncology, Harvard Medical School, Boston, Massachusetts., Shamji AF; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts. pclemons@broadinstitute.org stuart_schreiber@harvard.edu ashamji@broadinstitute.org., Clemons PA; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts. pclemons@broadinstitute.org stuart_schreiber@harvard.edu ashamji@broadinstitute.org., Schreiber SL; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts. |
| المصدر: | Cancer discovery [Cancer Discov] 2015 Nov; Vol. 5 (11), pp. 1210-23. Date of Electronic Publication: 2015 Oct 19. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research |
| مواضيع طبية MeSH: | Drug Screening Assays, Antitumor* , Small Molecule Libraries*, Computational Biology/*methods , Drug Resistance, Neoplasm/*genetics , Gene Expression Regulation, Neoplastic/*drug effects , Neoplasms/*genetics, Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cluster Analysis ; Datasets as Topic ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Mutation ; Neoplasms/drug therapy ; Protein Kinase Inhibitors/pharmacology |
| مستخلص: | Unlabelled: Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2). Significance: We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses. (©2015 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | United States HHMI_ Howard Hughes Medical Institute; RC2 CA148399 United States CA NCI NIH HHS; U01 CA176152 United States CA NCI NIH HHS; U01CA176152 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Protein Kinase Inhibitors) 0 (Small Molecule Libraries) |
| تواريخ الأحداث: | Date Created: 20151021 Date Completed: 20160819 Latest Revision: 20220129 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC4631646 |
| DOI: | 10.1158/2159-8290.CD-15-0235 |
| PMID: | 26482930 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2159-8290 |
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| DOI: | 10.1158/2159-8290.CD-15-0235 |