HIF, hypoxia and the role of angiogenesis in non-small cell lung cancer.
BACKGROUND
The role of angiogenesis in the initiation and progression of NSCLC and the molecular alterations leading to the growth of tumor vasculature are areas of great interest and recent therapeutic success.


METHODS
VEGF and its receptors play critical roles in the development of tumor vasculature and can be targeted by agents such as bevacizumab in the treatment of NSCLC. Furthermore, tumor hypoxia and the expression of the hypoxia-inducible factor (HIF) family of proteins are also linked to poorer survival in these patients. Recent studies using genetically engineered mouse models expressing stabilized HIF validate the importance of HIF in the evolution of NSCLC and demonstrate genetically that HIF is involved in NSCLC.


RESULTS
An overview of the key pathways and mediators of tumor angiogenesis, their relevance to the pathogenesis of NSCLC, and an update on the current status of angiogenesis inhibitors in NSCLC.


CONCLUSIONS
Angiogenesis is a key mediator of NSCLC progression. Several antiangiogenic strategies are in clinical use and under development. While candidate predictive biomarkers of response to antiangiogenic therapy exist, they await independent and prospective validation.
Jackson
Autumn L
AL
The University of North Carolina, The Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7295, USA.
Zhou
Bing
B
Kim
William Y
WY
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D051793:Hypoxia-Inducible Factor 1