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lüll Hypoxia inducible factor-1alpha as a cancer drug target Powis G; Kirkpatrick LMol Cancer Ther 2004[May]; 3 (5): 647-54The hypoxia inducible factor 1 (HIF-1) is a heterodimeric transcription factor that is an important regulator of the growing tumor's response to hypoxia. HIF-1 activity in tumors depends on the availability of the HIF-1alpha subunit, the levels of which increase under hypoxic conditions and through the activation of oncogenes and/or inactivation of tumor suppressor genes. HIF-1 activates genes that allow the cancer cell to survive and grow in the hostile hypoxic tumor environment. Increased tumor HIF-1alpha has been correlated with increased angiogenesis, aggressive tumor growth, and poor patient prognosis, leading to the current interest in HIF-1alpha as a cancer drug target. A number of anticancer agents have been reported to decrease HIF-1alpha or HIF-1 transactivating activity in cells in culture. However, more relevant to the agents' antitumor activity is whether HIF-1 is inhibited in tumors in vivo. This has been demonstrated for only a few of the reported HIF-1 inhibitors. Some of the agents are moving toward clinical trial where it will be important to demonstrate that the agents inhibit HIF-1alpha in patient tumors or, failing this, the downstream consequences of HIF-1 inhibition such as decreased vascular endothelial growth factor formation, and relate this inhibition to antitumor activity. Only in this way will it be possible to determine if HIF-1alpha is a valid cancer drug target in humans.|Antineoplastic Agents/pharmacology/therapeutic use[MESH]|Cell Hypoxia/genetics/physiology[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit[MESH]|Neoplasms/*drug therapy/*metabolism[MESH]|Signal Transduction[MESH]|Transcription Factors/antagonists & inhibitors/genetics/*metabolism[MESH]|Transcriptional Activation[MESH] |