Hypoxic environments occur normally at high altitude, or in underground burrows and in deep sea habitats. They also occur pathologically in human ischemia and in hypoxic solid tumors. Hypoxia in various cancer types and its related molecular mechanisms are associated with a poor clinical outcome. This review will discuss how hypoxia can influence two aspects of tumorigenesis, namely the direct, cell-intrinsic oncogenic effects, as well as the indirect effects on tumor progression mediated by an altered tumor microenvironment. We will also discuss recent progress in identifying the functional roles of hypoxia-related factors (HIFs), along with their regulators and downstream target genes, in cancer stem cells and therapy. Importantly, we propose, using convergent evolution schemes to identify novel biomarkers for both hypoxia adaptation and hypoxic solid tumors as an important strategy in the future.

中文翻译：

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缺氧与癌症相关的病理。

低氧环境通常发生在高海拔地区，地下洞穴和深海栖息地中。它们还以病理方式发生在人局部缺血和缺氧实体瘤中。各种癌症类型的缺氧及其相关的分子机制与不良的临床预后相关。这篇综述将讨论缺氧如何影响肿瘤发生的两个方面，即直接的细胞内致癌作用，以及改变的肿瘤微环境介导的对肿瘤进展的间接作用。我们还将讨论在鉴定缺氧相关因子（HIF）及其调节剂和下游靶基因在癌症干细胞和治疗中的功能方面的最新进展。重要的是，我们建议