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E-GEOD-37915 - Predicting drug responsiveness in humans cancers using genetically engineered mice

Status
Released on 1 January 2014, last updated on 2 June 2014
Organism
Mus musculus
Samples (38)
Array (1)
Protocols (12)
Description
Anti-cancer drug testing is challenging, but genetically engineered mouse models (GEMMs) and orthotopic, syngeneic transplants (OSTs) may offer advantages for pre-clinical testing including an intact microenvironment. We examined the efficacy of six chemotherapeutic or targeted anti-cancer drugs, alone and in combination, using over 500 GEMMs/OSTs representing three distinct breast cancer subtypes: Basal-like (C3(1)-T-antigen GEMM), Luminal B (MMTV-Neu GEMM), and Claudin-low (T11/TP53-/- OST). While a few single agents offered exceptional efficacy like lapatinib in the Neu/ERBB2 driven model, combination therapies tended to be more active and life prolonging. Using expression profiling of chemotherapy treated murine tumors, we identified an expression signature that was able to predict pathological complete response to neoadjuvant anthracycline-taxane treated human breast cancer patients, even after accounting for the common clinical variables and other genomic signatures. These results show that credentialed murine models can predict the efficacy of would-be anti-cancer compounds in humans, and that GEMMs can be used to develop new biomarkers of therapeutic responsiveness in humans. control X treatment
Experiment type
transcription profiling by array 
Contacts
Charles Perou <cperou@med.unc.edu>, Charles M Perou, Jerry Usary
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-37915.idf.txt
Sample and data relationshipE-GEOD-37915.sdrf.txt
Processed data (1)E-GEOD-37915.processed.1.zip
Array designA-MEXP-724.adf.txt
Links