1. Subtype and pathway specific responses to anticancer compounds in breast cancer
- Author
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Heidi S. Feiler, Eric A. Collisson, Joel Greshock, Mary Ann Hardwicke, Elizabeth Purdom, Gordon B. Mills, Bryan T. Hennessy, Lakshmi Jakkula, Pete Smith, Yinghui Guan, James E. Korkola, John W. Park, Joe W. Gray, Nicholas J. Wang, William J. Gibb, Kurtis E. Bachman, Denise M. Wolf, Lyubomir T. Vassilev, Henrik Bengtsson, Kenneth Wood, Stephen C. Benz, Zhi Hu, Anguraj Sadanandam, Nora Bayani, François Pepin, Frances Tong, Terence P. Speed, Laura M. Heiser, Sam Ng, Steffen Durinck, Theodore C. Goldstein, Joshua M. Stuart, Wen-Lin Kuo, Richard M. Neve, Paul T. Spellman, Jessica Billig, David Haussler, Sophia Lewis, Safiyyah Ziyad, Richard Wooster, Andrea Dueregger, Pierre Neuvial, Laurence J. Marton, Life Science Division [LBNL Berkeley], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Department of Biomolecular Engineering, University of California [Santa Cruz] (UCSC), University of California-University of California, Center for Biomolecular Science and Engineering, Department of Statistics [Berkeley], University of California [Berkeley], Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Department of Epidemiology and Biostatistics, University of California, San Francisco, University of California [San Francisco] (UCSF), Cytokinetics Inc, Oncology, Millenium Pharmaceuticals, Hoffmann-La Roche Ltd, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, The University of Texas M.D. Anderson Cancer Center [Houston], GlaxoSmithKline, Glaxo Smith Kline, Division of Hematology-Oncology, Progen Pharmaceuticals, The Walter and Eliza Hall Institute of Medical Research (WEHI), The Walter and Eliza Hall Institute of Medical Research, Howard Hughes Medical Institute [Santa Cruz] (HHMI), Center for Biomolecular Science & Engineering, Department of Computer Science [Alabama], University of Alabama [Tuscaloosa] (UA), University of California-University of California-Howard Hughes Medical Institute (HHMI), University of California [Santa Cruz] (UC Santa Cruz), University of California (UC)-University of California (UC), University of California [Berkeley] (UC Berkeley), University of California [San Francisco] (UC San Francisco), F. Hoffmann-La Roche [Basel], and Howard Hughes Medical Institute (HHMI)-University of California [Santa Cruz] (UC Santa Cruz)
- Subjects
Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,Gene Dosage ,Antineoplastic Agents ,Breast Neoplasms ,Genomics ,Biology ,Pharmacology ,Models, Biological ,Gene dosage ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Breast cancer cell line ,Transcription (biology) ,Cell Line, Tumor ,medicine ,Drug response ,Humans ,Breast Cancer Special Feature ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,medicine.disease ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,3. Good health ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Drug Screening Assays, Antitumor ,Signal transduction ,Signal Transduction - Abstract
International audience; Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.
- Published
- 2012