The article discusses the impact of oxygen availability on human cancer, focusing on hypoxia, a condition of low oxygen levels in tumors. Hypoxia is associated with altered cellular metabolism, increased resistance to radiation and chemotherapy, and plays a central role in tumor growth, angiogenesis, and metastasis. Hypoxia-inducible factors (HIFs) are key regulators of these processes, modulating tumor cell metabolism, angiogenesis, and growth. The discovery of HIFs in the 1990s provided insights into how cells sense and respond to oxygen deprivation, leading to the identification of HIF-1α, HIF-2α, and HIF-3α as critical regulators of hypoxia. HIFs are heterodimeric transcription factors that bind to hypoxia response elements (HREs) and regulate the expression of genes involved in angiogenesis, erythropoiesis, and other cellular processes. HIF-1α is particularly important in cancer progression, with its overexpression linked to poor patient outcomes in various malignancies. HIF-2α and HIF-3α also play roles in cancer, with HIF-2α promoting tumor growth and HIF-3α acting as a dominant negative regulator. HIFs influence cancer progression by modulating metabolic pathways, angiogenesis, and metastasis. They also impact the response to therapy, with hypoxic cells being more resistant to radiation and chemotherapy. Understanding the molecular mechanisms of HIF regulation has led to the development of therapeutic strategies targeting HIF pathways, including inhibitors of HIF accumulation and HIF target genes such as VEGF. These approaches aim to improve treatment outcomes by overcoming hypoxia-induced resistance. The role of hypoxia in cancer has been extensively studied, with research highlighting the importance of measuring and imaging hypoxia in tumors for better therapeutic strategies. Advances in understanding HIFs and their regulation have opened new avenues for developing targeted therapies that address hypoxia-related resistance and improve cancer treatment.The article discusses the impact of oxygen availability on human cancer, focusing on hypoxia, a condition of low oxygen levels in tumors. Hypoxia is associated with altered cellular metabolism, increased resistance to radiation and chemotherapy, and plays a central role in tumor growth, angiogenesis, and metastasis. Hypoxia-inducible factors (HIFs) are key regulators of these processes, modulating tumor cell metabolism, angiogenesis, and growth. The discovery of HIFs in the 1990s provided insights into how cells sense and respond to oxygen deprivation, leading to the identification of HIF-1α, HIF-2α, and HIF-3α as critical regulators of hypoxia. HIFs are heterodimeric transcription factors that bind to hypoxia response elements (HREs) and regulate the expression of genes involved in angiogenesis, erythropoiesis, and other cellular processes. HIF-1α is particularly important in cancer progression, with its overexpression linked to poor patient outcomes in various malignancies. HIF-2α and HIF-3α also play roles in cancer, with HIF-2α promoting tumor growth and HIF-3α acting as a dominant negative regulator. HIFs influence cancer progression by modulating metabolic pathways, angiogenesis, and metastasis. They also impact the response to therapy, with hypoxic cells being more resistant to radiation and chemotherapy. Understanding the molecular mechanisms of HIF regulation has led to the development of therapeutic strategies targeting HIF pathways, including inhibitors of HIF accumulation and HIF target genes such as VEGF. These approaches aim to improve treatment outcomes by overcoming hypoxia-induced resistance. The role of hypoxia in cancer has been extensively studied, with research highlighting the importance of measuring and imaging hypoxia in tumors for better therapeutic strategies. Advances in understanding HIFs and their regulation have opened new avenues for developing targeted therapies that address hypoxia-related resistance and improve cancer treatment.