An Integration of Complementary Strategies for Gene-Expression Analysis to Reveal Novel Therapeutic Opportunities for Breast Cancer

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dc.contributor.author Bild, Andrea H en_US
dc.contributor.author Parker, Joel S en_US
dc.contributor.author Gustafson, Adam M en_US
dc.contributor.author Acharya, Chaitanya R en_US
dc.contributor.author Hoadley, Katherine A en_US
dc.contributor.author Anders, Carey en_US
dc.contributor.author Marcom, P Kelly en_US
dc.contributor.author Carey, Lisa A en_US
dc.contributor.author Potti, Anil en_US
dc.contributor.author Nevins, Joseph R en_US
dc.contributor.author Perou, Charles M en_US
dc.date.accessioned 2012-01-12T17:19:48Z
dc.date.available 2012-01-12T17:19:48Z
dc.date.copyright 2009 en_US
dc.date.issued 2009-7-28 en_US
dc.identifier.citation Bild, Andrea H, Joel S Parker, Adam M Gustafson, Chaitanya R Acharya, Katherine A Hoadley, Carey Anders, P Kelly Marcom, Lisa A Carey, Anil Potti, Joseph R Nevins, Charles M Perou. "An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer" Breast Cancer Research: BCR 11(4):R55. (2009) en_US
dc.identifier.issn 1465-542X en_US
dc.identifier.uri http://hdl.handle.net/2144/3390
dc.description.abstract INTRODUCTION. Perhaps the major challenge in developing more effective therapeutic strategies for the treatment of breast cancer patients is confronting the heterogeneity of the disease, recognizing that breast cancer is not one disease but multiple disorders with distinct underlying mechanisms. Gene-expression profiling studies have been used to dissect this complexity, and our previous studies identified a series of intrinsic subtypes of breast cancer that define distinct populations of patients with respect to survival. Additional work has also used signatures of oncogenic pathway deregulation to dissect breast cancer heterogeneity as well as to suggest therapeutic opportunities linked to pathway activation. METHODS. We used genomic analyses to identify relations between breast cancer subtypes, pathway deregulation, and drug sensitivity. For these studies, we use three independent breast cancer gene-expression data sets to measure an individual tumor phenotype. Correlation between pathway status and subtype are examined and linked to predictions for response to conventional chemotherapies. RESULTS. We reveal patterns of pathway activation characteristic of each molecular breast cancer subtype, including within the more aggressive subtypes in which novel therapeutic opportunities are critically needed. Whereas some oncogenic pathways have high correlations to breast cancer subtype (RAS, CTNNB1, p53, HER1), others have high variability of activity within a specific subtype (MYC, E2F3, SRC), reflecting biology independent of common clinical factors. Additionally, we combined these analyses with predictions of sensitivity to commonly used cytotoxic chemotherapies to provide additional opportunities for therapeutics specific to the intrinsic subtype that might be better aligned with the characteristics of the individual patient. CONCLUSIONS. Genomic analyses can be used to dissect the heterogeneity of breast cancer. We use an integrated analysis of breast cancer that combines independent methods of genomic analyses to highlight the complexity of signaling pathways underlying different breast cancer phenotypes and to identify optimal therapeutic opportunities. en_US
dc.description.sponsorship V Foundation for Cancer Research (Partners in Excellence grant) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2009 Bild; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title An Integration of Complementary Strategies for Gene-Expression Analysis to Reveal Novel Therapeutic Opportunities for Breast Cancer en_US
dc.type article en_US
dc.identifier.doi 10.1186/bcr2344 en_US
dc.identifier.pubmedid 19638211 en_US
dc.identifier.pmcid 2750116 en_US

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