Gibbs Benjamin K, Sourbier Carole
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Methods Mol Biol. 2018;1709:129-137. doi: 10.1007/978-1-4939-7477-1_10.
Heat shock protein 90 (HSP90) is a molecular chaperone necessary for the folding and proper function of multiple "client" proteins. HSP90 is involved in numerous biological processes and is critical to maintain proteostasis and to protect the cells from potentially harmful environmental stresses such as heat. However, in cancer, the role of HSP90, and other molecular chaperones, is corrupted as many of HSP90 clients are kinases and transcription factors whose aberrant activation or mutation drives tumor growth. Thus, developing a polytherapy, or combination therapy, that includes an HSP90 inhibitor in addition to targeting an oncogene or oncogenic pathway is an appealing therapeutic approach. This protocol will provide detailed methods on how to assess the potential synergy of polytherapy by viability assays in vitro.
热休克蛋白90（HSP90）是一种分子伴侣，对于多种“客户”蛋白的折叠和正常功能至关重要。HSP90参与众多生物学过程，对于维持蛋白质稳态以及保护细胞免受诸如热等潜在有害环境应激至关重要。然而，在癌症中，HSP90以及其他分子伴侣的作用被破坏，因为许多HSP90客户蛋白是激酶和转录因子，其异常激活或突变会驱动肿瘤生长。因此，开发一种除了靶向癌基因或致癌途径外还包括HSP90抑制剂的联合疗法或组合疗法是一种有吸引力的治疗方法。本方案将提供关于如何通过体外活力测定评估联合疗法潜在协同作用的详细方法。
