Subtype and pathway specific responses to anticancer compounds in breast cancer

Laura M. Heiser, Anguraj Sadanandam, Wen Lin Kuo, Stephen C. Benz, Theodore C. Goldstein, Sam Ng, William J. Gibb, Nicholas Wang, Safiyyah Ziyad, Frances Tong, Nora Bayani, Zhi Hu, Jessica I. Billig, Andrea Dueregger, Sophia Lewis, Lakshmi Jakkula, James E. Korkola, Steffen Durinck, Franco̧is Pepin, Yinghui GuanElizabeth Purdom, Pierre Neuvial, Henrik Bengtsson, Kenneth W. Wood, Peter G. Smith, Lyubomir T. Vassilev, Bryan T. Hennessy, Joel Greshock, Kurtis E. Bachman, Mary Ann Hardwicke, John W. Park, Laurence J. Marton, Denise M. Wolf, Eric A. Collisson, Richard M. Neve, Gordon B. Mills, Terence P. Speed, Heidi S. Feiler, F. Wooster Richard, David Haussler, Joshua M. Stuart, Joe W. Gray, Paul T. Spellman

Research output: Contribution to journalArticle

274 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2724-2729
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number8
DOIs
StatePublished - Feb 21 2012

Keywords

  • Genomics
  • Predictor
  • Therapeutics

ASJC Scopus subject areas

  • General

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  • Cite this

    Heiser, L. M., Sadanandam, A., Kuo, W. L., Benz, S. C., Goldstein, T. C., Ng, S., Gibb, W. J., Wang, N., Ziyad, S., Tong, F., Bayani, N., Hu, Z., Billig, J. I., Dueregger, A., Lewis, S., Jakkula, L., Korkola, J. E., Durinck, S., Pepin, F., ... Spellman, P. T. (2012). Subtype and pathway specific responses to anticancer compounds in breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 109(8), 2724-2729. https://doi.org/10.1073/pnas.1018854108