缺氧诱导因子1和缺氧诱导因子2抑制剂靶向治疗癌症的研究进展

摘要

Hypoxia often occurs in chronic and acute vascular diseases and tumor formation.Hypoxia-inducible factor (HIF)-1 and HIF-2 are the core regulatory factors in maintaining the hypoxic microenvironment,and play an important role in the pathogenesis,development of cancer.HIF-1 and HIF-2 facilitate the resistance to chemotherapy,proliferation,metastasis and the invasive potential,all of which culminate in a decrease in patient survival.In addition,its inhibitors are also important in the targeted therapy of cancer.These inhibitors interfere with HIF mRNA expression,protein synthesis,protein degradation,DNA binding and transcriptional activity.In the treatment of cancer since 1996,no agents directly inhibiting HIFs have been approved for treating cancer patients.Therefore,it is important to summarize and develop a targeted anticancer drugs that inhibits both HIF-1 and HIF-2,which can prolong the survival of advanced cancer patients.%缺氧常发生在急慢性血管疾病、肿瘤形成中.而缺氧诱导因子(HIF)-1和HIF-2是维持肿瘤缺氧微环境的关键作用因子,在癌症的发生、发展中起重要的调节作用,可引起治疗耐受、生长增殖、侵袭转移,最终导致患者的生存期缩短.此外,其抑制剂在癌症的靶向治疗中也具有重要意义.这些抑制剂干扰了HIF的信使RNA表达、蛋白质合成、蛋白质降解以及DNA结合和转录.从1996年开始至今的癌症治疗中,并没有直接抑制HIFs的药物应用于临床.因此,总结并开发同时抑制HIF-1和HIF-2的靶向抗癌药物,对于延长晚期癌症患者的生存期具有重要意义.