Fig. 5

Selective radiosensitization of EML4-ALK oncogene addicted tumors exemplified by crizotinib. A schematic overview of another study conducted in frame of the KFO-214 evaluating the impact of the first generation ALK inhibitor crizotinib on tumor response to radiotherapy [30]. Different tumor cell lines were profiled for their addiction to ALK signaling by western (ALK activation) and FISH (ALK translocation). Crizotinib was originally intended to target cMET, hence cMET signaling was also investigated in all evaluated cell lines. Comprehensive in-vivo tumor growth delay studies revealed selective radiosensitzation of ALK addicted NSCLC cell lines. This was in line with synergistic effects of dual combination observed after photon orcarbon irradiation, respectively, by clonogenic survival assay and isobologram analysis. Together with data reported on second-generation ALK inhibitor TAE684 here, our data support the combination of this class of agents with radiotherapy in ALK addicted NSCLC