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Using breast (cancer) cell lines to measure bortezomib therapy response

ABSTRACT: Revealing targeted therapy for human cancer by gene module maps A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor prognosis “wound signature” is strongly associated with induction of a proteasome gene module. Inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed breast cells expressing the wound signature. Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies. Keywords: Gene expression profiling, breast cancer, therapy response, in vitro

ORGANISM(S): Homo sapiens

PROVIDER: GSE5307 | GEO | 2007/07/14

SECONDARY ACCESSION(S): PRJNA96313

REPOSITORIES: GEO

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Using breast (cancer) cell lines to measure bortezomib therapy response

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