染色质重塑复合体抑制剂在肿瘤治疗中的作用

Role of Chromatin Remodeling Complex Inhibitors in Tumour Therapy

CBL0137作为一种组蛋白分子伴侣的小分子抑制剂,以染色质重塑复合体(facilitates chromatin transcription,FACT)为靶点,可在不造成DNA损伤的情况下,通过抑制FACT促染色质转录活性,下调NF-κB,激活p53,从而抑制肿瘤的生物活性,通过调节DNA复制、DNA损伤修复和转录在多种癌症中发挥关键作用,并且在非小细胞肺癌、胰腺癌、乳腺癌和神经母细胞瘤中具有强大的抗肿瘤活性。文章综述FACT组成特征及功能、抑制FACT在肿瘤治疗中的药物作用机制,阐述CBL0137在多种恶性肿瘤中的应用,并对CBL0137在恶性肿瘤治疗中的应用前景进行总结和展望。

CBL0137,a small molecule inhibitor of histone chaperones,targets facilitates chromatin transcription(FACT)and suppresses tumour biological activity by inhibiting FACT,downregulating NF-κB and activating p53 without causing DNA damage.CBL0137 plays a key role in a variety of cancers by regulating DNA replication,repair and transcription,and exerts strong antitumor activity in non-small cell lung cancer,pancreatic cancer,breast cancer and neuroblastoma.This article reviews the composition and function of FACT,the mechanism of drug action through inhibiting FACT in tumour therapy and the application of CBL0137 in various malignant tumors,and summarizes the prospects of CBL0137 in malignant tumour treatment.