Regarding the effect on local tumour control in UT-SCC-15, there was no benefit seen by the simultaneous ErbB family inhibition with BIBW 2992 during fractionated irradiation (Figure3). tumour models for BIBW 2992 application alone. However, substantial 7-BIA intertumoural heterogeneity could be seen. In the UT-SCC-14, UT-SCC-15 and A431 tumour models a total regression of the tumours and no recurrence during treatment time (73 days) were determined where as for the A7 tumour only a slight effect was noticeable. For the combined treatment of fractionated radiotherapy (15f/15d) and BIBW 2992 administration a significant effect on tumour growth time was seen compared to irradiation alone for A7, UT-SCC-15 and A431 (ER 1.2 3.7), this advantage could not be demonstrated for FaDu and UT-SCC-14. However, the local tumour control was not altered for the UT-SCC-15 tumour model when adding BIBW 2992 to fractionated irradiation (30f/6weeks). == Conclusion == A heterogeneous effect on tumour growth time of 7-BIA BIBW 2992 alone as well as in combination with fractionated irradiation could be demonstrated for all tumour models. However, the significant effect on tumour growth time did not translate into an improvement of local tumour control for the UT-SCC-15 tumour model. Keywords:Combined treatment, Molecular targeting, EGFR/ErbB-inhibition, Fractionated 7-BIA irradiation, Local tumour control, BIBW 2992 == Introduction == Overexpression of the epidermal growth factor receptor (EGFR) on tumour cells has been shown to increase chemo- and radioresistance and therefore is associated with a poor outcome [1-3]. Inhibition of the EGFR in combination with radiotherapy has become a promising strategy to overcome this resistance. While anti-EGFR antibodies like cetuximab have the potential to prolong tumour growth and improve local tumour control when applied simultaneously to irradiation [4-10], for tyrosine kinase inhibitors (TKI), e.g. Erlotinib, the prolongation of tumour growth time did not translate into improved curative effects [1,8,11]. Clinical evaluation of EGFR-TK inhibition in combination with chemo- or radiotherapy revealed also heterogeneous effects [1,12]. One reason for the rather minor effects of TKI on local ATF3 tumour control could be that through heterodimerisation with other receptors of the EGFR-family, e.g. ErbB2, signaltransduction is still possible and therefore exclusively blocking the EGFR-TK is not 7-BIA sufficient [13-15]. Targeting more than one receptor of the EGFR-family might therefore show a therapeutic benefit. BIBW 2992 is an irreversible ErbB-family (EGFR/ErbB2/ErbB4) inhibitor, which in previous experiments demonstrated a significant prolongation of tumour growth time in a combined setting with single dose irradiation in FaDu tumour xenografts. In vitro but not in vivo a radiosensitizing effect could be shown for this tumour model. The antiproliferative effects are in line with a clear G0/G1 arrest of the tumour cells [16]. Based on these findings, the aim of the current study was to investigate the effect of BIBW 2992 with or without fractionated irradiation on tumour growth in five different human tumour xenografts (A7, A431, FaDu, UT-SCC-14 and UT-SCC-15). Consecutively, after these first experiments a local tumour control experiment was performed in the tumour model with the greatest effect on tumour growth time (UT-SCC-15). == Material and methods == == Animals and tumours == 7 to14-week-old male and female NMRI (nu/nu) mice from the specific pathogen-free animal breeding facility of the Experimental Center of the Medical Faculty Carl Gustav Carus, Technische Universitt Dresden were used for the experiments. The facility veterinarians checked the microbiological status of the animals regularly. The experiments and animal facilities were approved according to the German animal welfare regulations. Water ad libitum and a commercial 7-BIA laboratory animal diet were provided for the animals. A constant temperature of 26C, daylight in addition to a 12 h light12h dark electric cycle (light-on time 07.00 a.m.) and a relative humidity of 50-60% were supplied within the animal room. A whole-body irradiation 2 5 days before tumour transplantation with 4 Gy using 200 kV X-rays (0.5 mm Cu) at a dose rate of about 1 Gy/min was given for further immunosuppression of the animals. Four established human squamous cell carcinoma lines (FaDu, UT-SCC-14, UT-SCC-15, A431) and a glioma cell line (A7) were used in this study. UT-SCC-14 and UT-SCC-15 were established by Prof. Reidar Grenman (University of Turku, Finland). UT-SCC-14 [17,18] was derived from a squamous cell carcinoma of the tongue, UT-SCC-15 [17] is a tumour cell line originating of a recurrent tumour of the tongue. FaDu is an undifferentiated tumour of the hypopharynx [6,17,19-21], originally obtained from the American Type Culture.