靶向HSF1在肿瘤治疗中的作用

目前许多热休克蛋白90抑制剂已经用于抗癌的临床试验,这些抑制剂的产生是肿瘤治疗的里程碑,为癌症治疗探索出更多的新方法。高度保守的热休克转录因子1(heat shock factor 1, HSF1)作为转录因子促进热休克蛋白基因的转录和表达,肿瘤细胞比正常细胞更依赖其功能, HSF1对肿瘤的起始和维持是必需的：调控肿瘤细胞异常信号,抑制有丝分裂增加基因组非整倍性,抑制肿瘤细胞发生凋亡和促进肿瘤细胞转移和代谢等。随着很多小分子药物筛选方法不断的发现和运用,目前已有部分以HSF1为靶点的化合物研究报道,主要有槲皮素和雷公藤内酯抑制HSF1,同时减少热休克反应。文章综述了以HSF1为靶点的药物的研究前沿,并分别阐述了这类药物作用特点和机制。

Targeting HSF1 in Cancer Therapy

Recently, many heat shock protein 90 inhibitors have been used against cancers in clinical trials. Discovery of these inhibitors is a milestone for cancer treatment, with more therapeu-tic programs for cancers developed. Cancer cells are more dependent on the function of highly con-served HSF1, which, as a transcript factor, can promote the transcription and expression of HSF. HSF1 is essential for the initial and development of cancers, which can regulate the abnormal sig-ning in cancer cells, inhibit the aneuploidy increased by cell mitosis and apoptosis of cancer cells and promote the metastasis and metabolism of cancer cells. With the development and application of screening methods for small molecule drugs, compounds targeting HSF1 have been reported, inclu-ding quercetin and triptolide. Here, we review the advances in the studies on HSF1-targeting drugs and elucidate the characteristics and mechanism of this type of drugs.