Subtype and pathway specific responses to anticancer compounds in breast cancer

Laura M. Heiser(Lawrence Berkeley National Laboratory), Anguraj Sadanandam(Lawrence Berkeley National Laboratory), Wen‐Lin Kuo(Lawrence Berkeley National Laboratory), Stephen C. Benz(University of California, Santa Cruz), Theodore C. Goldstein(University of California, Santa Cruz), Sam Ng(University of California, Santa Cruz), William J. Gibb(Lawrence Berkeley National Laboratory), Nicholas J. Wang(Lawrence Berkeley National Laboratory), Safiyyah Ziyad(Lawrence Berkeley National Laboratory), Frances Tong(University of California, Berkeley), Nora Bayani(Lawrence Berkeley National Laboratory), Zhi Hu(Lawrence Berkeley National Laboratory), Jessica I. Billig(Lawrence Berkeley National Laboratory), Andrea Dueregger(Lawrence Berkeley National Laboratory), Sophia Lewis(Lawrence Berkeley National Laboratory), Lakshmi R. Jakkula(Lawrence Berkeley National Laboratory), James E. Korkola(Lawrence Berkeley National Laboratory), Steffen Durinck(Lawrence Berkeley National Laboratory), François Pépin(Lawrence Berkeley National Laboratory), Yinghui Guan(Lawrence Berkeley National Laboratory), Elizabeth Purdom(University of California, Berkeley), Pierre Neuvial(University of California, Berkeley), Henrik Bengtsson(University of California, Berkeley), Kenneth W. Wood(Cytokinetics (United States)), Peter G. Smith, Lyubomir T. Vassilev(La Roche College), Bryan T. Hennessy(The University of Texas MD Anderson Cancer Center), Joel Greshock(GlaxoSmithKline (United States)), Kurtis E. Bachman(GlaxoSmithKline (United States)), Mary Ann Hardwicke(GlaxoSmithKline (United States)), John W. Park(University of California, San Francisco), Laurence J. Marton, Denise M. Wolf(Lawrence Berkeley National Laboratory), Eric A. Collisson(University of California, San Francisco), Richard M. Neve(Lawrence Berkeley National Laboratory), Gordon B. Mills(The University of Texas MD Anderson Cancer Center), Terence P. Speed(Walter and Eliza Hall Institute of Medical Research), Heidi S. Feiler(Lawrence Berkeley National Laboratory), Richard Wooster(GlaxoSmithKline (United States)), David Haussler(University of California, Santa Cruz), Joshua M. Stuart(University of California, Santa Cruz), Joe W. Gray(Lawrence Berkeley National Laboratory), Paul T. Spellman(Lawrence Berkeley National Laboratory)
Proceedings of the National Academy of Sciences
October 14, 2011
10.1073/pnas.1018854108
Cited by 504

Abstract

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.

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