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 is 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 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 treatment with traditional chemotherapy, radiation, and hormonal therapy have not been effective. The recent development of molecularly target agents have 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.

VEGF and HIF in renal cell carcinogenesis / Minardi, Daniele; Lucarini, Guendalina; D’Anzeo, G.; Conti, Alessandro; DI PRIMIO, Roberto; Montironi, Rodolfo; Muzzonigro, Giovanni. - In: RECENT PATENTS ON BIOMARKERS. - ISSN 2210-3090. - 1:(2011), pp. 60-67.

VEGF and HIF in renal cell carcinogenesis.

MINARDI, Daniele;LUCARINI, Guendalina;CONTI, ALESSANDRO;DI PRIMIO, Roberto;MONTIRONI, RODOLFO;MUZZONIGRO, GIOVANNI
2011-01-01

Abstract

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 is 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 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 treatment with traditional chemotherapy, radiation, and hormonal therapy have not been effective. The recent development of molecularly target agents have 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.
2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/64376
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