TY - JOUR
T1 - Hypoxia inducible factor-1α as a cancer drug target
AU - Powis, Garth
AU - Kirkpatrick, Lynn
PY - 2004/5
Y1 - 2004/5
N2 - The 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-1α 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-1α has been correlated with increased angiogenesis, aggressive tumor growth, and poor patient prognosis, leading to the current interest in HIF-1α as a cancer drug target. A number of anticancer agents have been reported to decrease HIF-1α 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-1α 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-1α is a valid cancer drug target in humans.
AB - The 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-1α 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-1α has been correlated with increased angiogenesis, aggressive tumor growth, and poor patient prognosis, leading to the current interest in HIF-1α as a cancer drug target. A number of anticancer agents have been reported to decrease HIF-1α 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-1α 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-1α is a valid cancer drug target in humans.
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M3 - Short survey
C2 - 15141023
AN - SCOPUS:4444311880
SN - 1535-7163
VL - 3
SP - 647
EP - 654
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 5
ER -