Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, University of Burgundy, Dijon, France.
Cancer Lett. 2012 Dec 28;325(2):117-24. doi: 10.1016/j.canlet.2012.06.003. Epub 2012 Jun 28.
HSP70 is a chaperone that accumulates in the cells after many different stresses promoting cell survival in response to the adverse conditions. In contrast to normal cells, most cancer cells abundantly express HSP70 at the basal level to resist to various insults at different stages of tumorigenesis and during anti-cancer treatment. This cancer cells addiction for HSP70 is the rational for its targeting in cancer therapy. Much effort has been dedicated in the last years for the active search of HSP70 inhibitors. Additionally, the recent clinical trials on highly promising inhibitors of another stress protein, HSP90, showed compensatory increase in HSP70 levels and raised the question of necessity to combine HSP90 inhibitors with simultaneous inhibition of HSP70. Here we analyzed the recent advancement in creation of novel HSP70 inhibitors and different strategies for their use in anti-cancer therapy.
HSP70 是一种伴侣蛋白，在受到多种不同应激后会在细胞中积累，从而促进细胞存活以应对不利条件。与正常细胞不同，大多数癌细胞在基础水平上大量表达 HSP70，以抵抗肿瘤发生的不同阶段和抗癌治疗过程中的各种损伤。癌细胞对 HSP70 的这种依赖性为其在癌症治疗中的靶向提供了依据。在过去的几年中，人们一直在积极寻找 HSP70 抑制剂。此外，最近对另一种应激蛋白 HSP90 的高潜力抑制剂的临床试验显示，HSP70 水平代偿性增加，这引发了一个问题，即是否有必要将 HSP90 抑制剂与 HSP70 的同时抑制联合使用。在这里，我们分析了最近在新型 HSP70 抑制剂的创造方面取得的进展，以及将其用于癌症治疗的不同策略。
