Mechanisms of HIF-1α Function in Malignant Cells and Associated Therapeutic Strategies

Hypoxia-inducible factor 1-alpha (HIF-1α/HIF1A) is a transcription factor that responds to hypoxia and various other stimuli. HIF-1α plays a pivotal role in cellular adaptation to low oxygen levels by regulating the expression of genes involved in angiogenesis, glycolysis, and erythropoiesis. It activates pathways that enable cell survival under hypoxic conditions, which is essential for processes such as wound healing and tumor progression, and when the proliferation rate of tumors is particularly fast, leading to a decline in oxygen levels. HIF-1α is significantly upregulated in tumor cells and promotes cell invasion, which has been highlighted with the regulatory role of hypoxia in tumor growth by inhibiting apoptosis and tumor cell migration, giving tumor-associated HIF-1α a pro-, and antitumor role in the tumor microenvironment. This context has prompted the development of promising therapeutic strategies targeting cancer, and summarizes clinical trials of HIF-1α-based targeted drugs, immunotherapies, and nanoparticle-based therapies. In summary, this review examined the role and mechanisms of HIF-1α in cancer, emphasizing potential biomarkers and therapeutic targets associated with tumorigenesis.