651. Subtype and pathway specific responses to anticancer compounds in breast cancer.
- Author
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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, Wooster RF, Haussler D, Stuart JM, Gray JW, and Spellman PT
- Subjects
- Breast Neoplasms genetics, Cell Line, Tumor, Drug Screening Assays, Antitumor, Female, Gene Dosage genetics, Humans, Models, Biological, Signal Transduction genetics, Transcription, Genetic drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Breast Neoplasms classification, Breast Neoplasms drug therapy, Signal Transduction drug effects
- 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.
- Published
- 2012
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