title: VEGF and VEGFR genotyping in the prediction of clinical outcome for HCC patients receiving sorafenib: the ALICE-1 study.
abstract: Although new treatment modalities changed the global approach to hepatocellular carcinoma (HCC), this disease still represents a medical challenge. Currently, the therapeutic stronghold is sorafenib, a tyrosine kinase inhibitor (TKI) directed against the vascular endothelial growth factor (VEGF) family. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and thus tumour growth control. The aim of our study was to evaluate the role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. From a multicentre experience 148 samples (tumour or blood samples) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients' progression-free survival (PFS) and overall survival (OS) were analysed. At univariate analysis VEGF-A alleles C of rs25648, T of rs833061, C of rs699947, C of rs2010963, VEGF-C alleles T of rs4604006, G of rs664393, VEGFR-2 alleles C of rs2071559, C of rs2305948 were significant predictors of PFS and OS. At multivariate analysis rs2010963, rs4604006 and BCLC (Barcelona Clinic Liver Cancer) stage resulted to be independent factors influencing PFS and OS. Once prospectively validated, the analysis of VEGF and VEGFR SNPs may represent a clinical tool to better identify HCC patients more likely to benefit from sorafenib. On the other hand, the availability of more accurate predictive factors could help avoiding unnecessary toxicities to potentially resistant patients who may be optimal candidates for different treatments interfering with other tumour molecular pathways.
authors: Department of Medical Oncology Translational Oncology Unit AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
authors: Mario
authors: M
authors: Scartozzi
authors: Luca
authors: L
authors: Faloppi
authors: Gianluca
authors: G
authors: Svegliati Baroni
authors: Cristian
authors: C
authors: Loretelli
authors: Fabio
authors: F
authors: Piscaglia
authors: Massimo
authors: M
authors: Iavarone
authors: Pierluigi
authors: P
authors: Toniutto
authors: Giammarco
authors: G
authors: Fava
authors: Samuele
authors: S
authors: De Minicis
authors: Alessandra
authors: A
authors: Mandolesi
authors: Maristella
authors: M
authors: Bianconi
authors: Riccardo
authors: R
authors: Giampieri
authors: Alessandro
authors: A
authors: Granito
authors: Floriana
authors: F
authors: Facchetti
authors: Davide
authors: D
authors: Bitetto
authors: Sara
authors: S
authors: Marinelli
authors: Laura
authors: L
authors: Venerandi
authors: Sara
authors: S
authors: Vavassori
authors: Stefano
authors: S
authors: Gemini
authors: Antonietta
authors: A
authors: D'Errico
authors: Massimo
authors: M
authors: Colombo
authors: Luigi
authors: L
authors: Bolondi
authors: Italo
authors: I
authors: Bearzi
authors: Antonio
authors: A
authors: Benedetti
authors: Stefano
authors: S
authors: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D042583:Lymphangiogenesis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D009536:Niacinamide; D000077157:Sorafenib; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: VEGF; angiogenesis; hepatocellular carcinoma; rs2010963; rs4604006; single nucleotide polymorphisms; sorafenib