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Genomic and proteomic approaches to renal cell carcinoma
- Source :
- JN. Journal of Nephrology (Milano, 1992) 13 (2010): 155–164. doi:10.5301/JN.2010.90, info:cnr-pdr/source/autori:Zacchia M.; Vilasi A.; Capasso A.; Morelli F.; De Vita F.; Capasso G./titolo:Genomic and proteomic approaches to renal cell carcinoma/doi:10.5301%2FJN.2010.90/rivista:JN. Journal of Nephrology (Milano, 1992)/anno:2010/pagina_da:155/pagina_a:164/intervallo_pagine:155–164/volume:13, Europe PubMed Central
- Publication Year :
- 2010
- Publisher :
- SAGE Publications, 2010.
-
Abstract
- Renal cell carcinoma (RCC) is a frequent adult malignancy comprising different subtypes, with clear cell renal cell carcinoma (CCRCC) the most common. CCRCC is associated with the loss of function of the von Hippel-Lindau (VHL) gene. pVHL, the product of the VHL gene, is a component of an E3 ubiquitin ligase complex which targets proteins for degradation. In the absence of functional pVHL, a series of proteins accumulate in the cells, including hypoxic-inducible factor-1a (HIF-1a) and the products of the target genes of pVHL, such as vascular endothelial growth factor (VEGF). The activation of this pathway explains the use of both VEGF and VEGF-receptor inhibitors (bevacizumab, sunitinib and sorafenib) in the therapy of advanced CCRCC. In addition, mammalian target of rapamycin (mTOR), an intracellular serine/threonine kinase, is also implicated in HIF-1a regulation, thus reinforcing the rationale for using mTOR inhibitors (rapamycin) in CCRCC. Proteomic technologies have been applied to human renal cancer to detect biomarkers able to guide physicians for diagnostic and prognostic purposes. Among others, vimentin, heat shock protein 27 (Hsp27), annexin IV and serum amyloid alpha-1 (SAA-1) have been identified as reliable markers of RCC that are potentially useful in the clinical setting. Renal cell carcinoma (RCC) is a frequent adult malignancy comprising different subtypes, with clear cell renal cell carcinoma (CCRCC) the most common. CCRCC is associated with the loss of function of the von Hippel-Lindau (VHL) gene. pVHL, the product of the VHL gene, is a component of an E3 ubiquitin ligase complex which targets proteins for degradation. In the absence of functional pVHL, a series of proteins accumulate in the cells, including hypoxic-inducible factor-1α (HIF-1α) and the products of the target genes of pVHL, such as vascular endothelial growth factor (VEGF). The activation of this pathway explains the use of both VEGF and VEGF-receptor inhibitors (bevacizumab, sunitinib and sorafenib) in the therapy of advanced CCRCC. In addition, mammalian target of rapamycin (mTOR), an intracellular serine/threonine kinase, is also implicated in HIF-1α regulation, thus reinforcing the rationale for using mTOR inhibitors (rapamycin) in CCRCC. Proteomic technologies have been applied to human renal cancer to detect biomarkers able to guide physicians for diagnostic and prognostic purposes. Among others, vimentin, heat shock protein 27 (Hsp27), annexin IV and serum amyloid alpha-1 (SAA-1) have been identified as reliable markers of RCC that are potentially useful in the clinical setting. © 2011 Società Italiana di Nefrologia.
- Subjects :
- Proteomics
Sorafenib
urologic and male genital diseases
chemistry.chemical_compound
Renal cell carcinoma
Biomarkers, Tumor
medicine
Humans
Carcinoma, Renal Cell
PI3K/AKT/mTOR pathway
biology
business.industry
Sunitinib
Proteomic
Cancer
DNA, Neoplasm
Genomics
Prognosis
medicine.disease
Kidney Neoplasms
female genital diseases and pregnancy complications
Ubiquitin ligase
Gene Expression Regulation, Neoplastic
Vascular endothelial growth factor
Clear cell renal cell carcinoma
chemistry
Nephrology
Genomic
biology.protein
Cancer research
business
medicine.drug
Subjects
Details
- ISSN :
- 11218428
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of Nephrology
- Accession number :
- edsair.doi.dedup.....02ce7f1b6f777025d26d296e5943ed58