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Overview
Hypoxia (a low concentration of oxygen) occurs at the earliest stages of tumor growth. Hypoxic cells stimulate cellular responses such as altered glucose metabolism, inhibited apoptosis, increased angiogenesis and metastasis. All of these responses are mediated through the protein, hypoxia-inducible factor-1α (HIF-1α). While HIF-1α protein is found in a wide variety of human primary tumors, it is only produced at very low levels in normal tissue, making it a good target for cancer drug development.
Examples of human tumors that contain a large fraction of hypoxic cells are tumors of the head and neck, carcinoma of the cervix, soft tissue sarcomas, breast, and lung cancer. Other tumors, particularly renal cell carcinomas, express elevated HIF levels even in the absence of hypoxia.
Hypoxic tumor cells are resistant to radiation and, because of a decreased proliferation rate, are also resistant to many cancer drugs that target cell division. These cells may contribute to patient relapse after initial cancer treatment. Because of the important role that HIF-1α plays in regulating the response of growing tumors to hypoxia, the protein is expected to have substantial value as a target for therapeutic intervention.
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