Detalle Publicación


Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib.

Autores: Jiménez-Fonseca, P. (Autor de correspondencia); Martín, M. N. ; Carmona-Bayonas, A. ; Calvo González, Alfonso; Fernández-Mateos, J. ; Redrado Jordán, Miriam; Capdevila, J. ; Lago, N. M. ; Lacasta, A. ; Muñarriz, J. ; Segura, A. ; Fuster, J. ; Barón, F. ; LLanos, M. ; Serrano, R. ; Castillo, A. ; Cruz-Hernández, J. J. ; Grande, E.
Título de la revista: ONCOTARGET
ISSN: 1949-2553
Volumen: 9
Número: 97
Páginas: 36894 - 36905
Fecha de publicación: 2018
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.