Mitsiades Constantine S
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Natl Compr Canc Netw. 2004 Nov;2 Suppl 4:S23-7.
Multiple myeloma and Waldenström's macroglobulinemia are 2 presently incurable plasma cell dyscrasias with clinicopathological similarities, as well as distinct differences. Bortezomib, a prototypic boronic dipeptide proteasome inhibitor, was recently approved for the treatment of relapsed refractory multiple myeloma. Its efficacy in this poor prognosis clinical setting has raised the possibility that proteasome inhibition may also be suitable for the treatment of other plasma cell disorders, such as Waldenstrom's macroglobulinemia. Herein, we review the principles underlying the use of gene expression profiling for delineation of the mechanisms of action of bortezomib against plasma cell dyscrasias, as well as for identification of potential predictors of the clinical activity of bortezomib. We also discuss how transcriptional profile data from tumor cells of bortezomib-treated patients can help build preclinical predictors of responsiveness to proteasome inhibition with the ultimate goal to develop prognostic models that will facilitate the rational design of a patient-specific therapeutic algorithm for bortezomib treatment.
多发性骨髓瘤和华氏巨球蛋白血症是目前两种无法治愈的浆细胞发育异常疾病，它们在临床病理方面既有相似之处，也有明显差异。硼替佐米是一种典型的硼酸二肽蛋白酶体抑制剂，最近被批准用于治疗复发难治性多发性骨髓瘤。其在这种预后不良的临床情况下的疗效引发了一种可能性，即蛋白酶体抑制也可能适用于治疗其他浆细胞疾病，如华氏巨球蛋白血症。在此，我们回顾了利用基因表达谱来描绘硼替佐米针对浆细胞发育异常的作用机制以及识别硼替佐米临床活性潜在预测指标的相关原理。我们还讨论了来自硼替佐米治疗患者肿瘤细胞的转录谱数据如何有助于建立对蛋白酶体抑制反应性的临床前预测指标，最终目标是开发预后模型，以促进针对硼替佐米治疗的患者特异性治疗方案的合理设计。
