Abstract | PURPOSE: 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.
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Authors | Guilhem Bousquet, Mariana Varna, Irmine Ferreira, Li Wang, Pierre Mongiat-Artus, Christophe Leboeuf, Cédric de Bazelaire, Sandrine Faivre, Philippe Bertheau, Eric Raymond, Stéphane Germain, Anne Janin |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 72
Issue 6
Pg. 1183-93
(Dec 2013)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 24061866
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Antineoplastic Agents
- Biomarkers, Tumor
- Indoles
- Pyrroles
- Sunitinib
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Topics |
- Angiogenesis Inhibitors
(pharmacology)
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Biomarkers, Tumor
(metabolism)
- Breast Neoplasms
(drug therapy, pathology)
- Carcinoma, Renal Cell
(drug therapy, pathology)
- Cell Line, Tumor
- Endothelial Cells
(drug effects, metabolism)
- Female
- Humans
- Indoles
(pharmacology)
- Kidney Neoplasms
(drug therapy, pathology)
- Liver Neoplasms
(drug therapy, pathology)
- Mice
- Mice, Nude
- Molecular Targeted Therapy
- Pyrroles
(pharmacology)
- Sunitinib
- Xenograft Model Antitumor Assays
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