Tumor hypoxia: From basic knowledge to therapeutic implications

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 re-sponses and adaptations, as well as highlighting the effects and consequences of hypoxia, especially for angio-genesis 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 un-derstanding of the basics and the role of hypoxia in the tumor will help develop better therapeutic avenues in cancer treatment.

Automated summary

Hypoxia, characterized by diminished oxygen availability, has a significant impact on the tumor microenvironment, leading to abnormal vasculature, altered metabolism, and immune suppression. Limited effectiveness and development of resistance to anti-tumor therapy are also associated with hypoxia in the tumor microenvironment. This review summarizes the molecular mechanisms underlying hypoxic cellular responses and adaptations, and emphasizes the effects of hypoxia on angiogenesis, cellular metabolism, and immune suppression within the tumor microenvironment. Additionally, the recent advances in targeting hypoxia for therapeutic implications are discussed. A comprehensive understanding of hypoxia and its role in tumors will contribute to the development of improved cancer treatments.