Subtype and pathway specific responses to anticancer compounds in breast cancer.
Laura M Heiser
(1)
,
Anguraj Sadanandam
(1)
,
Wen-Lin Kuo
(1)
,
Stephen C Benz
(2, 3)
,
Theodore C Goldstein
(2, 3)
,
Sam Ng
(2, 3)
,
William J Gibb
(1)
,
Nicholas J Wang
,
Safiyyah Ziyad
(1)
,
Frances Tong
(4)
,
Nora Bayani
(1)
,
Zhi Hu
(1)
,
Jessica I Billig
(1)
,
Andrea Dueregger
(1)
,
Sophia Lewis
(1)
,
Lakshmi Jakkula
(1)
,
James E Korkola
(1)
,
Steffen Durinck
(1)
,
François Pepin
(1)
,
Yinghui Guan
(1)
,
Elizabeth Purdom
(4)
,
Pierre Neuvial
(5, 4)
,
Henrik Bengtsson
(4, 6)
,
Kenneth W Wood
(7)
,
Peter G Smith
(8)
,
Lyubomir T Vassilev
(9)
,
Bryan T Hennessy
(10)
,
Joel Greshock
(11)
,
Kurtis E Bachman
(11)
,
Mary Ann Hardwicke
(11)
,
John W Park
(12)
,
Laurence J Marton
(13)
,
Denise M Wolf
(1)
,
Eric A Collisson
(12)
,
Richard M Neve
(1)
,
Gordon B Mills
(10)
,
Terence P Speed
(14, 4)
,
Heidi S Feiler
(1)
,
Richard F Wooster
(11)
,
David Haussler
(15)
,
Joshua M Stuart
(2, 3)
,
Joe W Gray
(16)
,
Paul T Spellman
(1)
1
Life Science Division [LBNL Berkeley]
2 Department of Biomolecular Engineering
3 Center for Biomolecular Science and Engineering
4 Department of Statistics [Berkeley]
5 LSG - Laboratoire Statistique et Génome
6 UC San Francisco - University of California [San Francisco]
7 CI - Cytokinetics Inc
8 Oncology
9 F. Hoffmann-La Roche [Basel]
10 Department of Systems Biology, The University of Texas MD Anderson Cancer Center
11 GlaxoSmithKline
12 Division of Hematology-Oncology
13 Progen Pharmaceuticals
14 WEHI - The Walter and Eliza Hall Institute of Medical Research
15 HHMI - Howard Hughes Medical Institute [Santa Cruz]
16 Department of Computer Science [Alabama]
2 Department of Biomolecular Engineering
3 Center for Biomolecular Science and Engineering
4 Department of Statistics [Berkeley]
5 LSG - Laboratoire Statistique et Génome
6 UC San Francisco - University of California [San Francisco]
7 CI - Cytokinetics Inc
8 Oncology
9 F. Hoffmann-La Roche [Basel]
10 Department of Systems Biology, The University of Texas MD Anderson Cancer Center
11 GlaxoSmithKline
12 Division of Hematology-Oncology
13 Progen Pharmaceuticals
14 WEHI - The Walter and Eliza Hall Institute of Medical Research
15 HHMI - Howard Hughes Medical Institute [Santa Cruz]
16 Department of Computer Science [Alabama]
Nicholas J Wang
- Fonction : Auteur
Elizabeth Purdom
- Fonction : Auteur
- PersonId : 774999
- ORCID : 0000-0001-9455-7990
Pierre Neuvial
- Fonction : Auteur
- PersonId : 11
- IdHAL : pierre-neuvial
- ORCID : 0000-0003-3584-9998
Résumé
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.