Hypoxia in Tumor Microenvironment and Cellular Response

Hypoxia, a state commonly found in solid malignancies, is a characteristic of the tumor microenvironment (TME), which plays a significant role in the occurrence and progression of malignant tumors. Selective characteristics seen in the TME, such as the presence of cancer-associated fibroblasts (CAFs), unregulated extracellular matrix deposition, increased vascularization, and immune response suppression, frequently promote the progression of cancer. Apart from its influence on tumor invasion and metastasis, the hypoxic TME is crucial in triggering immunological suppression and resistance by promoting several modifications in the biology of stromal cells. Under such extended or intermittent hypoxic conditions, a number of chain reaction-like gene expression cascades known as the hypoxia-mediated gene regulatory network will be instigated, which will ultimately lead to the alteration of cellular behaviors and/or their cellular functions. Numerous research studies have indicated that hypoxia impairs the normal functioning of the cellular system. Research on the cellular response to hypoxia is currently a crucial area of study since it aids not only in the understanding of various signaling pathway modifications but also in the exploration of innovative therapeutic approaches. It is anticipated that investigating the molecular mechanism of hypoxia-mediated malignant tumor behavior and therapeutic target may yield novel concepts for anti-tumor therapeutics. Our review covers the impact of hypoxia on tumor behavior, as well as its relationships with immune cells and cell metabolism. Furthermore, we have reviewed the role of different components of TME which plays major part in cancer progression and development. We have also provided an overview of the effect of hypoxia on tumor oxidative stress and drug resistance.