Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cells. 2021 Mar 19;10(3):678. doi: 10.3390/cells10030678.
Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferating and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. The following review summarizes current literature regarding effects of hypoxia on DNA repair, metastasis, epithelial-to-mesenchymal transition, the cancer stem cell phenotype, and therapy resistance. We also discuss mechanisms and pathways, such as HIF signaling, mitochondrial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes. Finally, novel therapeutics that target the hypoxic tumor microenvironment or interfere with hypoxia-induced pathways are reviewed.
缺氧是实体瘤的一个常见特征，极大地阻碍了化疗、放疗和免疫治疗等常规癌症治疗的效果。增殖和晚期肿瘤中氧气的消耗导致一系列遗传、转录和代谢适应，促进了存活、转移和临床恶性表型。在这些相互关联的途径的交点是缺氧诱导因子（HIFs），它们在缺氧下协调转录反应。以下综述总结了关于缺氧对 DNA 修复、转移、上皮-间充质转化、癌症干细胞表型和治疗耐药性的影响的最新文献。我们还讨论了有助于缺氧诱导表型变化的机制和途径，如 HIF 信号、线粒体动力学、外泌体和未折叠蛋白反应。最后，还综述了靶向缺氧肿瘤微环境或干扰缺氧诱导途径的新型治疗方法。
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