School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
Chem Soc Rev. 2011 Aug;40(8):4307-17. doi: 10.1039/c1cs15032d. Epub 2011 Apr 11.
The adaptation of tumours to hypoxia is critical for their survival and growth. The high proliferation rate of solid tumours causes the continuous outstripping of the oxygen supply provided by the local vasculature, resulting in hypoxic regions within the tumour. Hypoxia inducible factor (HIF) is the key mediator of cellular response to hypoxia, activating the expression of multiple genes that participate in angiogenesis, iron metabolism, glycolysis, glucose transport and cell proliferation and survival. The critical role of the hypoxia response network and HIF in cancer has resulted in it being viewed as an ideal target for small molecule intervention. In this tutorial review we discuss the central role of HIF in the adaptation of tumours to a hypoxic environment, going on to describe recent attempts at developing small molecules that disrupt this pathway and their potential for use as the next generation anticancer therapeutics.
肿瘤对缺氧的适应对于其生存和生长至关重要。实体瘤的高增殖率导致其不断超越局部脉管系统提供的氧气供应，从而导致肿瘤内出现缺氧区域。缺氧诱导因子 (HIF) 是细胞对缺氧反应的关键介质，激活参与血管生成、铁代谢、糖酵解、葡萄糖转运以及细胞增殖和存活的多种基因的表达。缺氧反应网络和 HIF 在癌症中的关键作用使其被视为小分子干预的理想靶点。在本教程综述中，我们讨论了 HIF 在肿瘤适应缺氧环境中的核心作用，接着描述了最近开发破坏该途径的小分子的尝试及其作为下一代抗癌治疗药物的潜力。
