HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma
Maroto Rey, José Pablo (Institut d'Investigació Biomèdica Sant Pau)
Esteban, Emilio (Department of Oncology, Nuevo HUCA, Oviedo)
Parra, E. Fernández (Department of Oncology, H. U. Nuestra Señora de Valme, Sevilla)
Mendez-Vidal, M. J. (Department of Oncology, H. U. Reina Sofía, Córdoba)
Domènech, Montserrat (Fundació Althaia)
Pérez-Valderrama, Begoña (Department of Oncology, H. U. Virgen del Rocio, Sevilla)
Calderero, V (Department of Oncology, H. Fundación Miguel Servet, Zaragoza)
Pérez-Gracia, J. L. (Department of Oncology, Clinica Universitaria de Pamplona, Pamplona)
Grande, Enrique (Hospital Universitario Ramón y Cajal (Madrid))
Algaba, Ferran (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Fecha:	2017
Resumen:	Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival. Eighty-one patients were included: median PFS was 10. 8 months (95% CI: 7. 4-13. 5 months), median overall survival was 21. 8 months (95% CI: 14. 7-29. 8 months) and objective response rate was 40. 7%, with 7. 4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4. 3 vs 11. 5 months, hazard ratio =2. 64, 95% CI: 1. 03-6. 80, P =0. 036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5. 9 vs 10. 9 months, P =0. 263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome. These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials.
Derechos:	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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	C-myc ; Clear-cell renal cell carcinoma ; HIF ; Sunitinib
Publicado en:	OncoTargets and therapy, Vol. 10 (september 2017) , p. 4635-4643, ISSN 1178-6930

DOI: 10.2147/OTT.S137677
PMID: 29033582

9 p, 1.0 MB

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