IL-8 and eNOS polymorphisms predict bevacizumab-based first line treatment outcomes in RAS mutant metastatic colorectal cancer patients
| Autor: | Ettore Capoluongo, Ilaria Bossi, Alessia Mennitto, Concetta Santonocito, Filippo de Braud, Romano Danesi, Roberta Mennitto, Rosa Berenato, Giovanni Schinzari, Ernesto Rossi, Carlo Barone, Donatella Guarino, Mariantonietta Di Salvatore, Marzia Del Re, Marta Caporale, Filippo Pietrantonio, Michele Basso, Antonia Martinetti, Armando Orlandi |
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| Přispěvatelé: | Di Salvatore, M, Pietrantonio, F, Orlandi, A, Del Re, M, Berenato, R, Rossi, E, Caporale, M, Guarino, D, Martinetti, A, Basso, M, Mennitto, R, Santonocito, C, Mennitto, A, Schinzari, G, Bossi, I, Capoluongo, E, Danesi, R, de Braud, F, Barone, C |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Pathology Organoplatinum Compounds Colorectal cancer medicine.medical_treatment Leucovorin Angiogenesis Inhibitors law.invention Cohort Studies Single nucleotid polymorphism 0302 clinical medicine Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA law Enos Genotype Antineoplastic Combined Chemotherapy Protocols Medicine Neoplasm Metastasis Clinical pharmacology biology ENOS Treatment Outcome 030220 oncology & carcinogenesis Female Fluorouracil Colorectal Neoplasms medicine.drug Research Paper medicine.medical_specialty Bevacizumab Nitric Oxide Synthase Type III Single-nucleotide polymorphism bevacizumab Polymorphism Single Nucleotide 03 medical and health sciences IL-8 Single nucleotid polymorphisms Internal medicine Humans single nucleotid polymorphisms Aged Chemotherapy business.industry Interleukin-8 medicine.disease biology.organism_classification 030104 developmental biology Mutation ras Proteins business Pharmacogenetics |
| Zdroj: | Oncotarget |
| Popis: | // Mariantonietta Di Salvatore 1 , Filippo Pietrantonio 2 , Armando Orlandi 1 , Marzia Del Re 3 , Rosa Berenato 2 , Ernesto Rossi 1 , Marta Caporale 2 , Donatella Guarino 4 , Antonia Martinetti 2 , Michele Basso 1 , Roberta Mennitto 2 , Concetta Santonocito 4 , Alessia Mennitto 2 , Giovanni Schinzari 1 , Ilaria Bossi 2 , Ettore Capoluongo 4 , Romano Danesi 3 , Filippo de Braud 2 , Carlo Barone 1 1 Unit of Clinical Oncology, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy 2 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy 3 Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy 4 Laboratory of Clinical Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy Correspondence to: Mariantonietta Di Salvatore, email: mariantonietta.disalvatore@gmail.com Keywords: single nucleotid polymorphisms, bevacizumab, IL-8, eNOS, colorectal cancer Received: May 23, 2016 Accepted: November 02, 2016 Published: January 25, 2017 ABSTRACT Background : Predictive biomarkers of efficacy and toxicity of bevacizumab have not yet been validated. This study assessed the influence of IL-8, eNOS and VEGF-A polymorphisms in RAS mutated metastatic colorectal cancer patients receiving bevacizumab-based chemotherapy. Methods: 120 patients treated with first-line combination FOLFOX6 plus bevacizumab were included. A historical cohort of 112 RAS mutated colorectal cancer patients treated with FOLFOX6 alone served as control group. The following SNPs were analyzed: IL-8 c.-251T>A; eNOS c.-786T>C and c.-894G>T; VEGF-A c.936C>T, c.958T>C, c.1154A>G and c.2578C>A. Correlation of SNPs, baseline IL-8 serum levels and bevacizumab-efficacy was done. Results : In the bevacizumab group, carriers of the IL-8 alleles c.-251TA+AA showed a shorter PFS (P=0.002) and OS (P=0.03) compared to TT alleles. Patients with pre-treatment IL-8 18,25 pg/ml). IL-8 c.-251TA+AA carriers had significantly higher IL-8 levels (P T was found associated with higher severe toxicity (P=0.0002) in patients carrying the c.-894TT genotype. Conclusions : Although our data need prospective validation, IL-8 and eNOS SNPs may be have a role as predictive biomarkers for bevacizumab efficacy and toxicity. |
| Databáze: | OpenAIRE |
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