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 J. 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 Guan; Elizabeth 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

doi:10.1073/pnas.1018854108

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 J. 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 journal › Article › peer-review

358 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 language	English (US)
Pages (from-to)	2724-2729
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	109
Issue number	8
DOIs	https://doi.org/10.1073/pnas.1018854108
State	Published - Feb 21 2012

Keywords

Genomics
Predictor
Therapeutics

ASJC Scopus subject areas

General

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Heiser, L. M., Sadanandam, A., Kuo, W. L., Benz, S. C., Goldstein, T. C., Ng, S., Gibb, W. J., Wang, N. J., 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

Heiser, LM, Sadanandam, A, Kuo, WL, Benz, SC, Goldstein, TC, Ng, S, Gibb, WJ, Wang, NJ, Ziyad, S, Tong, F, Bayani, N, Hu, Z, Billig, JI, Dueregger, A, Lewis, S, Jakkula, L, Korkola, JE, Durinck, S, Pepin, F, Guan, Y, Purdom, E, Neuvial, P, Bengtsson, H, Wood, KW, Smith, PG, Vassilev, LT, Hennessy, BT, Greshock, J, Bachman, KE, Hardwicke, MA, Park, JW, Marton, LJ, Wolf, DM, Collisson, EA, Neve, RM, Mills, GB, Speed, TP, Feiler, HS, Richard, FW, Haussler, D, Stuart, JM, Gray, JW & Spellman, PT 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, vol. 109, no. 8, pp. 2724-2729. https://doi.org/10.1073/pnas.1018854108

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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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AU - Sadanandam, Anguraj

AU - Kuo, Wen Lin

AU - Benz, Stephen C.

AU - Goldstein, Theodore C.

AU - Ng, Sam

AU - Gibb, William J.

AU - Wang, Nicholas J.

AU - Ziyad, Safiyyah

AU - Tong, Frances

AU - Bayani, Nora

AU - Hu, Zhi

AU - Billig, Jessica I.

AU - Dueregger, Andrea

AU - Lewis, Sophia

AU - Jakkula, Lakshmi

AU - Korkola, James E.

AU - Durinck, Steffen

AU - Pepin, Franco̧is

AU - Guan, Yinghui

AU - Purdom, Elizabeth

AU - Neuvial, Pierre

AU - Bengtsson, Henrik

AU - Wood, Kenneth W.

AU - Smith, Peter G.

AU - Vassilev, Lyubomir T.

AU - Hennessy, Bryan T.

AU - Greshock, Joel

AU - Bachman, Kurtis E.

AU - Hardwicke, Mary Ann

AU - Park, John W.

AU - Marton, Laurence J.

AU - Wolf, Denise M.

AU - Collisson, Eric A.

AU - Neve, Richard M.

AU - Mills, Gordon B.

AU - Speed, Terence P.

AU - Feiler, Heidi S.

AU - Richard, F. Wooster

AU - Haussler, David

AU - Stuart, Joshua M.

AU - Gray, Joe W.

AU - Spellman, Paul T.

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AB - 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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Subtype and pathway specific responses to anticancer compounds in breast cancer

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