低氧与肿瘤治疗

Hypoxia and antitumor therapy

低氧是实体瘤的普遍现象,对肿瘤的增殖、凋亡、血管生成、浸润转移、能量代谢及放化疗抵抗性都具有重要的作用。本文回顾了两类针对低氧肿瘤的药物研发策略:作用于低氧诱导因子(hypoxia-inducible factors, HIFs)及其相关信号通路的分子靶向药物,以及靶向于肿瘤低氧微环境的低氧激活前药,分别列举了各个药物的设计思路和作用机制,对各种策略所面临的挑战与机遇进行了探讨。

Hypoxia is a common phenomenon of solid tumors and plays an important role in tumor proliferation, angiogenesis, invasion, metastasis, energy metabolism, resistance to chemotherapy and radiotherapy. In this paper, two approaches for targeting hypoxia in cancer therapy are reviewed. One is molecular targeted agents targeting HIFs and relative signal pathway and the other is hypoxia-activated prodrugs targeting tumor hypoxic microenvironment. Several example compounds with their design and mechanism are listed and the particular challenges and opportunities for each strategy are also discussed.