دورية أكاديمية
أعرض في EDS

Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma.

التفاصيل البيبلوغرافية
العنوان: Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma.
المؤلفون: Garcia-Donas, J, Leandro-García, L J, González Del Alba, A, Morente, M, Alemany, I, Esteban, E, Arranz, J A, Climent, M A, Gallardo, E, Castellano, D E, Bellmunt, J, Mellado, B, Puente, J, Moreno, F, Font, A, Hernando, S, Robledo Batanero, Mercedes, Rodriguez Antona, Cristina
المساهمون: Fundación Pfizer
بيانات النشر: Elsevier
سنة النشر: 2013
المجموعة: REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII)
مصطلحات موضوعية: Aged, 80 and over, Angiogenesis Inhibitors, Antineoplastic Agents, Basic Helix-Loop-Helix Transcription Factors, Biomarkers, Tumor, Carcinoma, Renal Cell, Cell Hypoxia, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Gene Expression, Humans, Hypoxia-Inducible Factor-Proline Dioxygenases, Immunohistochemistry, Indoles, Kidney Neoplasms, Male, Middle Aged, Neoplasm Metastasis, Prospective Studies, Pyrroles, RNA, Messenger, Sunitinib, Survival, Treatment Outcome
الوصف: BACKGROUND Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib. RESULTS High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023). CONCLUSIONS We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance. ; This study was supported by an unrestricted educational grant from Pfizer (SUT-REN-07) that played no role in study design, collection, analysis or interpretation of data, writing the report or the decision to submit the paper for publication. ; Sí
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 1569-8041
العلاقة: https://doi.org/10.1093/annonc/mdt219Test.; Ann Oncol . 2013;24(9):2409-14.; http://hdl.handle.net/20.500.12105/17502Test; Annals of oncology : official journal of the European Society for Medical Oncology
DOI: 10.1093/annonc/mdt219
الإتاحة: https://doi.org/20.500.12105/17502Test
https://doi.org/10.1093/annonc/mdt219Test
https://hdl.handle.net/20.500.12105/17502Test
حقوق: http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; open access
رقم الانضمام: edsbas.70355497
قاعدة البيانات: BASE
الوصف
تدمد:15698041
DOI:10.1093/annonc/mdt219