Division of Haematology, University of Messina, Messina, Italy.
Eur J Haematol. 2011 Feb;86(2):93-110. doi: 10.1111/j.1600-0609.2010.01558.x. Epub 2010 Dec 20.
Despite advances in understanding the molecular pathogenesis of multiple myeloma and promising new therapies, almost all patients eventually relapse with resistant disease. There is therefore a strong rationale for combining novel therapies that target intrinsic molecular pathways mediating multiple myeloma cell resistance. One such protein family is the heat shock proteins (HSP), especially the HSP90 family. Heat shock protein inhibitors have been identified as promising cancer treatments as, while they only inhibit a single biologic function, the chaperone-protein association, their effect is widespread as it results in the destruction of numerous client proteins. This article reviews the preclinical and clinical data, which support the testing of HSP90 inhibitors as cancer drugs and update the reader on the current status of the ongoing clinical trials of HSP90 inhibitors in multiple myeloma.
尽管在理解多发性骨髓瘤的分子发病机制和有前途的新疗法方面取得了进展，但几乎所有患者最终都会因耐药疾病而复发。因此，有充分的理由将针对介导多发性骨髓瘤细胞耐药性的内在分子途径的新型疗法联合起来。热休克蛋白（HSP）就是这样一个蛋白家族，特别是 HSP90 家族。热休克蛋白抑制剂已被确定为有前途的癌症治疗方法，因为虽然它们仅抑制单一的生物学功能（伴侣蛋白结合），但其效果广泛，因为它导致许多客户蛋白的破坏。本文综述了支持 HSP90 抑制剂作为癌症药物进行测试的临床前和临床数据，并更新了读者关于 HSP90 抑制剂在多发性骨髓瘤中正在进行的临床试验的最新情况。
