Tumor cell gene expression changes following short-term in vivo exposure to single agent chemotherapeutics are related to survival in multiple myeloma.
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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DOI：
10.1158/1078-0432.ccr-07-4568
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发表时间：
2008-08-01
期刊：
影响因子：
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通讯作者：
Shaughnessy JD Jr
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文献类型：
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作者：
Burington B;Barlogie B;Zhan F;Crowley J;Shaughnessy JD Jr
体内治疗后肿瘤细胞中整体基因表达模式的变化可能因治疗而异，并提供比治疗前基因表达谱（GEP）额外或协同的预后能力。这种药物-细胞相互作用的分子读数也可能指向作用/耐药机制。在新诊断的多发性骨髓瘤（MM）患者中，在使用地塞米松（n = 45）或沙利度胺（n = 42）进行体内治疗之前和48小时后获得肿瘤细胞的微阵列数据；对于复发的MM，在给药前（n = 36）和给药后（n = 19）获得微阵列数据。地塞米松和沙利度胺诱导肿瘤细胞常见和独特的GEP改变。在接受串联移植的新诊断MM患者中，基线和48小时基因亚群中GEP的综合变化（许多与氧化应激和细胞骨架动力学有关）可预测预后。来那度胺暴露后，沙利度胺改变的基因也发生了变化，并预测了接受来那度胺单药治疗的复发患者的无事件生存率和总生存率。结合基线分子特征，短期单药暴露后GEP的变化可能有助于指导MM患者的治疗决策。发现与生存相关的药物改变表达的基因可能指向与对不同类别药物的反应和/或耐药性相关的分子开关。
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.