Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106


Cancer Therapy By Targeting Hypoxia-Inducible Factor-1

Author(s): Y. Li, D. Ye.


Tumors are invariably less well-oxygenated than the normal tissues from which they arise. Hypoxia-inducible factor-1 (HIF-1), a key transcriptional regulator, plays a central role in the adaptation of tumor cells to hypoxia by activating the transcription of genes, which regulate several biological processes including angiogenesis, cell proliferation, survival, glucose metabolism and migration. The expression, activity and stability of HIF-1 are not only induced in response to reduced oxygen availability but also modulated through PI-3K, MAPKs, autocrine signaling pathways, E3 ubiquitin ligases, and other regulators. The regulators and effects of HIF-1 in cancer have intensively provided us a new clue for the HIF-1 targeting anticancer therapy. This review evaluates the HIF-1 structure, the regulation mechanisms, the functions in cancer and corresponding anticancer strategies.

Keywords: Cancer, hypoxia-inducible factor-1, angiogenesis, Warburg effects, tumor microenvironment, therapy, HIF-1, PI-3K, MAPKs, hypoxia-reoxygenation, oxygen-dependent degrada-tion domain, N-TAD, C-TAD, 26S proteasome, NLS, PAS-A, PAS-B, VHL, PHD, VEGF, oxygen partial pressure, Reactive Oxygen Species, EMSA, (E1), (E2), (E3), VHL-E3, pVHL (VHL protein), HAF, (EGFR), thioredoxin, hypoxia, (GLUT), PFK, ENO1, (GAPDH), c-Myc, CKIs, Cdk, Apoptosis, Metastasis, Chemotherapy, Radiotherapy, HRE, (EPO), TPT, RNA polymerase, Cyclin-dependent kinase, GPCR, oncogenes, Photodynamic Therapy, Bcl-2 expression

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Article Details

Year: 2010
Page: [782 - 796]
Pages: 15
DOI: 10.2174/156800910793605857
Price: $58