Journal
BRITISH JOURNAL OF CANCER
Volume 111, Issue 7, Pages 1310-1318Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.432
Keywords
SRC inhibition; dasatinib; cetuximab; radiation therapy; antagonistic effect
Categories
Funding
- Merck KgaA
- Spanish Association Against Cancer
- Barcelona Committee
- AGAUR from the Catalan Government (Spain) [SGR681]
Ask authors/readers for more resources
Background: Cetuximab is often combined with radiotherapy in advanced SCCHN. Alternative routes bypassing inhibition of EGFR with cetuximab may overshadow the efficacy of this combination. We undertook this study to investigate a possible role of dasatinib in this scenario. Methods: The SCC5, SCC25, SCC29, FaDu and A431 cell lines were assessed in vitro for cell proliferation under cetuximab and dasatinib treatments. In FaDu and A431 cells, dasatinib plus cetuximab resulted in higher proliferation than cetuximab alone. Then, FaDu and A431 cells were implanted into subcutaneous tissue of athymic mice that were irradiated with 30 Gy in 10 fractions over 2 weeks, and treated with cetuximab and dasatinib. Tumour growth, DNA synthesis and angiogenesis were determined. The EGFR, RAS-GTP activity, phosphorylated AKT, ERK1/2, SRC protein levels and VEGF secretion were determined in vitro. Results: The addition of dasatinib to cetuximab and radiotherapy increased tumour growth, DNA synthesis and angiogenesis that were associated with RAS, AKT and ERK1/2 activation, and SRC inhibition in FaDu and A431 cells. Conclusions: In xenografts derived from these two cell lines, dasatinib did not improve the efficacy of cetuximab combined with radiotherapy. On the contrary, it worsened tumour control achieved by the combination of these two treatments.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available