Differential regulation of sunitinib targets predicts its tumor-type-specific effect on endothelial and/or tumor cell apoptosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Chemotherapy and Pharmacology Année : 2013

Differential regulation of sunitinib targets predicts its tumor-type-specific effect on endothelial and/or tumor cell apoptosis

Guilhem Bousquet
  • Fonction : Auteur
Mariana Varna
  • Fonction : Auteur
Irmine Ferreira
  • Fonction : Auteur
Li Wang
Pierre Mongiat-Artus
  • Fonction : Auteur
Christophe Leboeuf
Cédric De Bazelaire
  • Fonction : Auteur
Sandrine Faivre
  • Fonction : Auteur
Philippe Bertheau
  • Fonction : Auteur
Eric Raymond
Anne Janin
  • Fonction : Auteur

Résumé

PURPOSE: Sunitinib is an inhibitor of tyrosine-kinase receptors, and no biomarker predictive of sunitinib response is available. The purpose of this preclinical study was to show whether sunitinib molecular targets could be used as biomarkers to assess tumor response to sunitinib in human cancer cell line xenografts of three different tumor types. METHODS: Using mice xenografted with liver, breast and renal carcinoma cell lines, we sequentially analyzed the effect of 7-day sunitinib treatment on tumor and vascular compartments. RESULTS: In all xenografts, microvessel damage occurred from Day 1. Tumor damage also occurred in liver, breast, but not in renal xenografts. Using specific human and mouse probes for genes encoding sunitinib targets, we showed a significant relation between apoptotic tumor cell numbers and human PDGFRΒ and RET mRNA expression in liver cancer and to human VEGFR2 expression in breast cancer xenografts. In contrast, in renal cancer xenografts, vascular effect evaluated by measuring endothelial cell apoptosis was related to mouse Vegfr1, Vegfr2 and Vegfa-164 expression. CONCLUSION: This study identifies sunitinib vascular and tumor effects according to different tumor types and shows that sunitinib molecular targets used as biomarkers enable assessment of therapeutic response.

Dates et versions

hal-02142772 , version 1 (28-05-2019)

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Citer

Guilhem Bousquet, Mariana Varna, Irmine Ferreira, Li Wang, Pierre Mongiat-Artus, et al.. Differential regulation of sunitinib targets predicts its tumor-type-specific effect on endothelial and/or tumor cell apoptosis. Cancer Chemotherapy and Pharmacology, 2013, 72 (6), pp.1183--1193. ⟨10.1007/s00280-013-2300-0⟩. ⟨hal-02142772⟩
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