VEGF and HIF in Renal Cell Carcinogenesis
d' Anzeo Gianluca,
Di Primio Roberto,
Seventy-five percent of all cases of renal cell carcinoma have clear cell histology (CCRCC). In CCRCC alterations of the promoter of the VHL gene are the defining somatic genetic event. The high vascularity of RCC suggests a fundamental role of angiogenesis to its pathogenesis and is deeply associated with proliferation and metastasis. Many HIF-α target genes appear to be involved in these pathways, targeting VEGF and resulting in angiogenesis, increased vascular permeability, endothelial cell (EC) proliferation, survival, migration, and differentiation and promotion of degradation of the extracellular matrix. Molecular markers might predict the responsiveness of molecular targeted therapy. While in case of localised disease, radical nephrectomy is a highly effective therapy, for locally invasive tumors, surgical approaches are less effective and not curative for metastatic disease. In advanced cases, immune systematic cytokine therapies have resulted in low response rates, with a smaller percentage exhibiting complete remission upon treatment. Systemic treatments with traditional chemotherapy, radiation, and hormonal therapy have not been effective. The recent development of molecularly target agents has radically changed the management of metastatic CCRCC and the availability of reliable biomarkers to monitor therapy response and of anti-angiogenic drugs evasive to resistance could render targeted therapy more effective. We also review current patents on diagnosis and treatments of renal cancer.
Keywords: HIF, VEGF, angiogenesis, kidney cancer, monoclonal antibodies, prognosis, therapy, Renal Cell Carcinogenesis, carcinoma, histology, metastasis, endothelial cell, radical nephrectomy, metastatic disease, chemotherapy, hypermethylation, von Hippel, hypoxia inducible factor, vascular endothelial growth factor, platelet derived growth factor, placental growth factor, cyclooxygenase-2, matrix metallo-proteinase 1, lysyl oxidase, chemotaxis, chemokine receptors, transforming growth factor, insulin-like growth, epidermal growth factor receptor, reactive oxygen species, computed tomography, tumor-associated macrophages, IFN, Bevacizumab, temsirolimus, Cathepsin
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