肿瘤内降低氧气供应，即所谓的低氧症，是癌症的最常见特征之一。低氧症通过一系列病理改变（如异常血管、代谢异常、免疫抑制表型等）将肿瘤微环境（TME）塑造成促癌和促转移的生态位。此外，新的证据表明，治疗的效果有限或产生抗药性可能很大程度上是由于低氧TME。本文将重点总结介绍介导低氧细胞反应和适应的分子机制，并突出低氧的影响和后果，尤其是对TME内的血管生成调节、细胞代谢变化和免疫抑制反应的影响。我们还概述通过靶向低氧在TME中的治疗意义和最新进展。深入了解低氧在肿瘤中的基础和角色将有助于开发更好的癌症治疗方法。版权所有 © 2023 Elsevier Ltd。

Diminished oxygen availability, termed hypoxia, within solid tumors is one of the most common characteristics of cancer. Hypoxia shapes the landscape of the tumor microenvironment (TME) into a pro-tumorigenic and pro-metastatic niche through arrays of pathological alterations such as abnormal vasculature, altered metabolism, immune-suppressive phenotype, etc. In addition, emerging evidence suggests that limited efficacy or the development of resistance towards antitumor therapy may be largely due to the hypoxic TME. This review will focus on summarizing the knowledge about the molecular machinery that mediates the hypoxic cellular responses and adaptations, as well as highlighting the effects and consequences of hypoxia, especially for angiogenesis regulation, cellular metabolism alteration, and immunosuppressive response within the TME. We also outline the current advances in novel therapeutic implications through targeting hypoxia in TME. A deep understanding of the basics and the role of hypoxia in the tumor will help develop better therapeutic avenues in cancer treatment.Copyright © 2023 Elsevier Ltd. All rights reserved.