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Título
Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib
Autor(es)
Materia
IL-6
Osteopontin
Pancreatic neuroendocrine tumors
Sunitinib
VEGFR-3
Clasificación UNESCO
3201.01 Oncología
Fecha de publicación
2018
Editor
Oncotarget
Citación
Jiménez-Fonseca P., Navarro Martín M., Carmona-Bayonas A., Calvo A., Fernández-Mateos J., Redrado M., Capdevila J., Martínez Lago N., Lacasta A., Muñarriz J., Segura ., Fuster J., Barón F., et al (2018) Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib. Oncotarget.; 9: 36894-36905.
Resumen
[EN]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.
URI
DOI
10.18632/oncotarget.26380
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