Fig. 5

Therapeutic efficacy of MET and EGFR inhibitors using the KCI-10-40 PDX model. A Characterization of the KCI-10-40X1 PDX model. KCI-10-40 primary GBM showed 29.5 % EGFR amplification (a, b). After the primary tumor was grown as a xenograft, neurosphere cells were derived for in vitro growth (c) which showed 100 % EGFR amplification (d). These cells induce intracranial tumor growth in the mouse brain (e and f). B KCI-10-40X1 cells express nestin, vimentin, and Sox2, as shown by immunofluorescence staining, indicating stem-cell-like properties. C KCI-10-40X1 tumors showed high sensitivity to erlotinib treatment (75 mg/kg); tumor regression could be seen after 1 week. However, after 5 weeks of continuous treatment at 100 mg/kg, tumors began to regrow much faster, indicating the start of acquired resistance. Note that KCI-10-40X1 took 2 weeks to reach 1000 mm³ in size, while the resistant tumor (KCI-10-40X1/erl) took almost 11 weeks to reach similar size. D Although KCI-10-40X1/erl tumors grow while on erlotinib treatment, discontinuing treatment (vehicle) accelerated tumor growth. V-4084 (100 mg/kg) alone did not inhibit KCI-10-40X1/erl tumor growth. E V-4084 (100 mg/kg) in combination with erlotinib (100 mg/kg) inhibited KCI-10-40X1/erl tumor growth