Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies

作者：Wei‐Fang Zuo, Qiwen Pang, Xinyu Zhu, Qianqian Yang, Qian Zhao, Gu He, Bo Han, Wei Huang · 发表于：Journal of Hematology & Oncology · 年份：2024 · DOI：10.1186/s13045-024-01601-1 · 被引用次数：75 · 研究领域：Heat shock proteins research、Protein Structure and Dynamics、Endoplasmic Reticulum Stress and Disease

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 ...