Dasatinib worsens the effect of cetuximab in combination with fractionated radiotherapy in FaDu- and A431-derived xenografted tumours
Baro, Marta (Institut Català d'Oncologia)
de Llobet, Lara I. (Institut Català d'Oncologia)
Figueras, Agnès (Institut Català d'Oncologia)
Skvortsova, Ira (Innsbruck Medical University)
Mesia, Ricard (Institut Català d'Oncologia)
Balart, Josep (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona. Departament de Medicina

Fecha:	2014
Resumen:	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. 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. 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. 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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Antagonistic effect ; Cetuximab ; Dasatinib ; Radiation therapy ; SRC inhibition
Publicado en:	British journal of cancer, Vol. 111 Núm. 7 (23 2014) , p. 1310-1318, ISSN 1532-1827

DOI: 10.1038/bjc.2014.432
PMID: 25077442

9 p, 1.6 MB

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