Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib
Jiménez-Fonseca, Paula (Medical Oncology Department, Hospital Universitario Central de Asturias)
Martín, Miguel Navarro (Instituto de Investigación Biomédica de Salamanca)
Carmona-Bayonas, Alberto (Hospital General Universitario Morales Meseguer (Múrcia))
Calvo, Alfonso (Clínica Universidad de Navarra. Centro de Investigación Médica Aplicada)
Fernández-Mateos, Javier (Complejo Asistencial Universitario de Salamanca. Instituto de Investigación Biomédica de Salamanca)
Redrado, Miriam (IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Department of Histology and Pathology, University of Navarra, Pamplona)
Capdevila Castillón, Jaume (Hospital Universitari Vall d'Hebron)
Lago, Nieves Martínez (Complejo Hospitalario Universitario de A Coruña)
Lacasta, Adelaida (Hospital Universitario de Donostia (Sant Sebastià, País Basc))
Muñarriz, Javier (Consorci Hospitalari Provincial de Castelló)
Segura, Ángel (Hospital Universitari i Politècnic La Fe (València))
Fuster, Josep (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Barón, Francisco (Complejo Hospitalario Universitario de Santiago de Compostela)
Llanos, Marta (Hospital Universitario de Canarias (La Laguna))
Serrano, Raquel (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Castillo, Alfredo (Hospital Universitario Central de Asturias)
Cruz Hernández, Juan Jesús (Instituto de Investigación Biomédica de Salamanca)
Grande, Enrique (Medical Oncology Department, MD Anderson Cancer Center)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Several circulating biomarkers and single nucleotide polymorphisms (SNPs) have been correlated with efficacy and tolerability to antiangiogenic agents. These associations remain unexplored in well-differentiated, metastatic pancreatic neuroendocrine tumors treated with the multitargeted tyrosine kinase inhibitor sunitinib. We have assessed the effect on tumor response at 6 months, overall survival, progression-free survival and safety of 14 SNPs, and 6 soluble proteins. Forty-three patients were recruited. Two SNPs in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene predicted lower overall survival: rs307826 with hazard ratio (HR) 3. 67 (confidence interval [CI] 95%, 1. 35-10. 00) and rs307821 with HR 3. 84 (CI 95%, 1. 47-10. 0). Interleukin-6 was associated with increased mortality: HR 1. 06 (CI 95%, 1. 01-1. 12), and osteopontin was associated with shorter PFS: HR 1. 087 (1. 01-1. 16), independently of Ki-67. Furthermore, levels of osteopontin remained higher at the end of the study in patients considered non-responders: 38. 5 ng/mL vs. responders: 18. 7 ng/mL, p-value=0. 039. Dynamic upward variations were also observed with respect to IL-8 levels in sunitinib-refractory individuals: 28. 5 pg/mL at baseline vs. 38. 3 pg/mL at 3 months, p-value=0. 024. In conclusion, two VEGFR-3 SNPs as well as various serum biomarkers were associated with diverse clinical outcomes in patients with well-differentiated pancreatic neuroendocrine tumors treated with sunitinib.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Sunitinib ; Osteopontin ; IL-6 ; VEGFR-3 ; Pancreatic neuroendocrine tumors
Published in:	Oncotarget, Vol. 9 (december 2018) , p. 36894-36905, ISSN 1949-2553

DOI: 10.18632/oncotarget.26380
PMID: 30651923

12 p, 2.4 MB

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