Hsp90分子抑制剂拮抗肿瘤耐药的研究进展

Hsp90作为热休克蛋白家族中的重要一员,是一种对细胞生存所必需的分子伴侣,它发挥着稳定顾客蛋白构象、维持其功能的作用。许多顾客蛋白在肿瘤中处于过度表达或持续激活状态,与肿瘤的发生发展有着密切的关系。因此,Hsp90在近年的研究中倍受关注,已经发展为抗肿瘤治疗的良好靶点,目前已经有多个Hsp90抑制剂进入临床实验。近年随着肿瘤分子生物学的研究,肿瘤分子靶向治疗已取得明显成果,针对多种癌症已获得了多个用于靶向治疗的单克隆抗体或小分子化学物质,如用于治疗某些HER2阳性乳腺癌的曲妥珠单抗、用于治疗NSCLC的吉非替尼等。然而随着这些药物的应用,肿瘤耐药性不可避免的产生。多方面研究表明Hsp90抑制剂会引起与耐药相关的多个分子的降解,提示其在拮抗耐药方面具有重要的意义。本文就Hsp90分子抑制剂在拮抗肿瘤耐药方面的研究进行综述。

Hsp90 Inhibitor and its Development in Antagonizing Tumor Resistance*

As an important member of Heat Shock Proteins, heat shock protein 90 （HSP90） is a molecular chaperone protein essential for cellular survival through sustaining the stability and function of a diverse range of client proteins. Many of the client proteins are highly expressed or over-activated in cancer cells, suggesting that it may be critically important for cancer cell growth and/or survival. Hence,Hsp90 has attracted much attention recently and become a major therapeutic target for cancer. There have been some Hsp90 inhibitors entered into clinical trial. In recent years, with the study of cancer molecular biology, molecularly targeted therapy has achieved significant advances in cancer therapy. Some monoclonal antibodies or small-molecule chemicals are designed for a variety of cancers, such as Trastuzumab using for HER2-positive breast cancer, Gefitinib for NSCLC treatment. But with the application of these drugs, cancer resistance inevitably generated. Various studies show that Hsp90 inhibitors may cause the degradation of multiple molecules associated with resistance, indicating that has an important significance in antagonizing resistance. Here we review the research of lisp90 inhibitor in drug-resistance treatment.