Abstract | BACKGROUND: METHODS: Radiosensitisation of several NSCLC cell lines by BMS-690514 was assessed in vitro using clonogenic assay and in vivo using nude mice. RESULTS: In vitro studies showed that BMS-690514 alone decreases clonogenic survival of NSCLC cells lines but no potential enhancement of IR response was observed in the combination. In tumour-bearing mice, BMS-690514 alone inhibits the growth of NSCLC xenografts, including the T790M mutation-harbouring H1975 tumour. The concomitant combination of BMS-690514 and radiation did not increase mice survival in comparison with treatment with IR alone. In contrast, BMS-690514 markedly enhances the anti-tumour effect of radiation in a sequential manner on H1299 and H1975 xenografts. Immunohistochemistry revealed a qualitative reduction in vessel area after administrations of BMS-690514, compared with vehicle-treated controls, suggesting that revascularisation may explain the schedule dependency of the tumour-growth delay observed. CONCLUSION: The results of association with radiation show that BMS-690514 may be a successful adjuvant to clinical radiotherapy. These findings are of translational importance because the clinical benefits of anti-EGFR and anti-VEGFR therapy might be schedule dependent.
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Authors | Y Loriot, P Mordant, N Dorvault, T De la motte Rouge, J Bourhis, J-C Soria, E Deutsch |
Journal | British journal of cancer
(Br J Cancer)
Vol. 103
Issue 3
Pg. 347-53
(Jul 27 2010)
ISSN: 1532-1827 [Electronic] England |
PMID | 20628392
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- BMS-690514
- Piperidines
- Pyrroles
- Triazines
- ErbB Receptors
- Receptors, Vascular Endothelial Growth Factor
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, genetics, pathology, radiotherapy)
- Cell Division
(drug effects, radiation effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Combined Modality Therapy
- Drug Screening Assays, Antitumor
- ErbB Receptors
(antagonists & inhibitors, genetics)
- Exons
- Humans
- Mice
- Mice, Nude
- Mutation
- Neoplasm Transplantation
- Piperidines
(therapeutic use)
- Pyrroles
(therapeutic use)
- Receptors, Vascular Endothelial Growth Factor
(antagonists & inhibitors)
- Sequence Deletion
- Transplantation, Heterologous
- Triazines
(therapeutic use)
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