缺氧和缺氧诱导因子1α:肿瘤转移的中心调控子

摘要

缺氧在大多数实体瘤中普遍存在,通常与预后不良具有相关性.作为缺氧诱导因子的功能亚基,缺氧诱导因子1α(HIF-1α)受氧浓度调控,它的高表达通常与肿瘤转移和较差的临床结局相关.最近的研究显示,肿瘤转移的每一个步骤,从最初的上皮细胞向间充质细胞的转变到最终的远处器官转移,都在缺氧的潜在调控之下,表明了缺氧和缺氧诱导因子在肿瘤转移中的主导地位.以缺氧和缺氧诱导因子为靶标的多种治疗措施,包括缺氧诱导因子抑制剂,缺氧激活的生物还原前体药物和基因疗法有望成为预防或减少肿瘤转移的有效手段.%Hypoxia is a common condition found in a wide range of solid tumors and is often associated with poor prognosis. As the function submit of HIF, HIF-1αundergo oxygen-dependent regulation, and its overexpression is frequently associated with metastasis and poor clinical outcomes. Recent studies show that each step of the tumor metastasis process , from the initial epithelial-mesenchymal transition to the ultimate organotropic colonization , can potentially he regulated by hypoxia, suggesting a master regulator role of hypoxia and HIFs in tumor metastasis. Multiple approaches to targeting hypoxia and HIFs,including HIF inhibitors,hypoxia-activated bioreductive prodrugs , and gene therapies may become effective treatments to prevent or reduce tumor metastasis.