Lung cancer is one of the malignant tumors with fastest growing rates in incidence and mortality in our country, also with largest threat to human health and life. However, the exact mechanisms underlying lung cancer development remain unclear. The microenvironment of tumor hypoxia was discovered in 1955, but hypoxia in lung cancer tissues had not been successfully detected till 2006. Further studies show that hypoxia not only functions through the resistance to radiotherapy, but also regulates lung cancer development, invasion, metastasis, chemotherapy resistance and prognosis through an important oncogene HIF (hypoxia inducible factor), with its regulators PHD (prolyl hydroxylase domain) and pVHL (product of von Hippel-Lindau gene). Therefore, hypoxia, HIF, PHD and pVHL should be considered as potential therapeutic targets for lung cancer pathogenesis and progression.
肺癌是我国发病率和死亡率增长最快，对人群健康和生命威胁最大的恶性肿瘤，其发生发展机制尚未完全清楚。肿瘤的低氧微环境发现于1955年，而肺癌组织低氧直至2006年才被成功检测到。随着研究的深入，低氧对肺癌的影响不仅限于对放疗的抵抗作用，而且还会通过一个重要的促癌分子低氧诱导因子（hypoxia inducible factor, HIF）以及其调节蛋白脯氨酸羟化酶（prolyl hydroxylase domain, PHD）和希佩尔•林道病基因产物（product of von Hippel-Lindau gene, pVHL）对肺癌的发生发展、侵袭转移、化疗耐药以及预后等产生重要的调节作用。因此，低氧、HIF、PHD和pVHL必将成为十分有潜力的肺癌治疗靶点。