Myeloma Institute for Research & Therapy, University of Arkansas for Medical Sciences, Little Rock, AZ 72205, USA.
Clin Lymphoma Myeloma Leuk. 2011 Jun;11 Suppl 1:S77-81. doi: 10.1016/j.clml.2011.03.027. Epub 2011 Apr 28.
The heat shock protein 90 (HSP90) family of proteins are ubiquitous molecular chaperones that are intricately involved in folding, activation, maturation, and assembly of many proteins that include essential mediators of signal transduction and cell cycle progression. They are abundant in eukaryotic cells and localized to the cytoplasm and mitochondria as well as the endoplasmic reticulum under normal conditions, making up 1% to 2% of all cellular proteins. HSP90 proteins have increased expression in a number of malignancies, including multiple myeloma. HSP90 inhibition can influence multiple oncogenic pathways and proteins involved in myeloma, therefore making it an attractive target for drug development in this disease. This article serves as an overview of the pre-clinical data and clinical trial data on HSP90 inhibitors in multiple myeloma.
热休克蛋白 90(HSP90)家族蛋白是普遍存在的分子伴侣,它们在许多蛋白质的折叠、激活、成熟和组装中起着错综复杂的作用,这些蛋白质包括信号转导和细胞周期进程的重要介质。它们在真核细胞中含量丰富,在正常条件下定位于细胞质和线粒体以及内质网,占所有细胞蛋白的 1%至 2%。HSP90 蛋白在多种恶性肿瘤中表达增加,包括多发性骨髓瘤。HSP90 抑制可以影响多发性骨髓瘤中涉及的多种致癌途径和蛋白质,因此使其成为该疾病药物开发的有吸引力的靶点。本文综述了 HSP90 抑制剂在多发性骨髓瘤中的临床前数据和临床试验数据。