Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents.

中文翻译：

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热休克蛋白作为癌症的标志：从分子机制到治疗策略的见解


热休克蛋白是重要的分子伴侣，在稳定蛋白质结构、促进受损蛋白质的修复或降解以及维持蛋白质稳态和细胞功能方面发挥着至关重要的作用。大量研究表明，热休克蛋白在癌症中高表达，与肿瘤的发生和进展密切相关。 “癌症标志”是癌症生物学的核心特征，它共同定义了细胞从正常状态转变为肿瘤生长状态时所获得的一系列功能特征，包括持续的增殖信号、逃避生长抑制剂、对肿瘤细胞的抵抗等。细胞死亡，实现复制永生、诱导血管生成以及激活侵袭和转移。热休克蛋白通过激活或抑制各种信号通路来调节癌症特征的关键作用已得到充分证明。因此，本文从癌症特征的角度概述了热休克蛋白在重要生物过程中的作用，并总结了针对热休克蛋白调节各种癌症特征的小分子抑制剂。此外，我们进一步讨论了涉及热休克蛋白和有前途的双靶点抑制剂的联合治疗策略，以强调靶向热休克蛋白用于癌症治疗的潜力。 综上所述，本综述强调了靶向热休克蛋白如何调控癌症的标志，这将为更好地阐明和理解热休克蛋白在肿瘤学中的作用以及癌症发生发展的机制提供有价值的信息，并有助于促进癌症的发展。更有效、毒性更小的新型抗癌药物。