Tumor Cell Gene Expression Changes Following Short-term In vivo Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma

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Abstract
Changes in global gene expression patterns in tumor cells following in vivo therapy may vary by treatment and provide added or synergistic prognostic power over pretherapy gene expression profiles (GEP). This molecular readout of drug-cell interaction may also point to mechanisms of action/resistance. In newly diagnosed patients with multiple myeloma (MM), microarray data were obtained on tumor cells prior to and 48 hours after in vivo treatment using dexamethasone (n = 45) or thalidomide (n = 42); in the case of relapsed MM, microarray data were obtained prior to (n = 36) and after (n = 19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes in tumor cells. Combined baseline and 48-hour changes in GEP in a subset of genes, many related to oxidative stress and cytoskeletal dynamics, were predictive of outcome in newly diagnosed MM patients receiving tandem transplants. Thalidomide-altered genes also changed following lenalidomide exposure and predicted event-free and overall survival in relapsed patients receiving lenalidomide as a single agent. Combined with baseline molecular features, changes in GEP following short-term single-agent exposure may help guide treatment decisions for patients with MM. Genes whose drug-altered expression were found to be related to survival may point to molecular switches related to response and/or resistance to different classes of drugs.