Additional file 10 of Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy

Additional file 10: Supplementary Fig.6. Combining capmatinib and RT is efficacious against human tumor cells without side effects. a, Western blots of PDOX tumors demonstrating complete inhibition of the autophosphorylation of TRIM24-MET and decrease of pERK and pAKT levels following three doses of 25mg/kg capmatinib (2 doses on day 1, one dose on day 2), compared to vehicle (veh) treatment. b, Representative IHC pictures of pERK and pAKT in two pairs of tumors treated with either vehicle or capmatinib. Scale=50µm, veh=vehicle, cap=capmatinib. c, BLI signals of all mice enrolled in the preclinical xenograft trial comparing cabozantinib to capmatinib. Each line represents one mouse. The ends of lines indicate the onset of neurological symptoms and thereby the endpoints. Treatment started on day 13. In contrast to all other treatments, capmatinib induced tumor regression in two of eight mice and stable disease in six out of eight mice. d, 3D chart of combinatorial in vitro trials, demonstrating radiation improves the efficacy of capmatinib and crizotinib in the tested concentrations. cap=capmatinib, cri=crizotinib, RT=radiation. e, Body weight curves of mice in the depicted 4-arm preclinical trial, starting from the first treatment. f, Development of total flux (radiance, p/sec/cm2/sr) derived from BLI measurements of the cranial and spine region of all vehicle-treated mice in the preclinical trial displayed in Figure 5C.