Abstract：
:The lack of markers to predict chemotherapy responses in patients poses a major handicap in cancer treatment. We searched for gene expression patterns that correlate with docetaxel or cisplatin response in a mouse model for breast cancer associated with BRCA1 deficiency. Array-based expression profiling did not identify a single marker gene predicting docetaxel response, despite an increase in Abcb1 (P-glycoprotein) expression that was sufficient to explain resistance in several poor responders. Intertumoral heterogeneity explained the inability to identify a predictive gene expression signature for docetaxel. To address this problem, we used a novel algorithm designed to detect differential gene expression in a subgroup of the poor responders that could identify tumors with increased Abcb1 transcript levels. In contrast, standard analytical tools, such as significance analysis of microarrays, detected a marker only if it correlated with response in a substantial fraction of tumors. For example, low expression of the Xist gene correlated with cisplatin hypersensitivity in most tumors, and it also predicted long recurrence-free survival of HER2-negative, stage III breast cancer patients treated with intensive platinum-based chemotherapy. Our findings may prove useful for selecting patients with high-risk breast cancer who could benefit from platinum-based therapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Rottenberg S,Vollebergh MA,de Hoon B,de Ronde J,Schouten PC,Kersbergen A,Zander SA,Pajic M,Jaspers JE,Jonkers M,Lodén M,Sol W,van der Burg E,Wesseling J,Gillet JP,Gottesman MM,Gribnau J,Wessels L,Linn SC,Jonkers J,doi
10.1158/0008-5472.CAN-11-4201subject
Has Abstractpub_date
2012-05-01 00:00:00pages
2350-61issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-4201journal_volume
72pub_type
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