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.

补充材料10：补充图6。卡马替尼（capmatinib）联合放射治疗（RT）可在无不良反应的前提下有效对抗人类肿瘤细胞。
a. 蛋白质免疫印迹（Western blots）结果：相较于溶剂（veh，vehicle）处理组，经25mg/kg剂量卡马替尼给药三次（第1天给药2次、第2天给药1次）的患者来源异种移植瘤（PDOX）样本中，TRIM24-MET的自磷酸化被完全抑制，磷酸化ERK（pERK）与磷酸化AKT（pAKT）的蛋白水平显著降低。
b. 免疫组化（IHC）典型图像：展示两组分别经溶剂与卡马替尼处理的肿瘤样本中pERK与pAKT的表达情况。标尺=50μm，veh=溶剂对照，cap=卡马替尼。
c. 生物发光成像（BLI）信号数据：收录了对比卡博替尼（cabozantinib）与卡马替尼疗效的临床前异种移植试验中所有受试小鼠的结果。每条曲线代表一只小鼠，曲线终点对应小鼠出现神经症状的时间，即试验终止节点。治疗于第13天启动。与其余所有处理组不同，卡马替尼使8只受试小鼠中的2只实现肿瘤消退，6只达到疾病稳定状态。
d. 组合体外试验三维图表：结果显示在本次测试的浓度范围内，放射治疗可提升卡马替尼与克唑替尼（crizotinib）的抗肿瘤活性。注：cap=卡马替尼，cri=克唑替尼，RT=放射治疗。
e. 受试小鼠体重变化曲线：对应本次四臂临床前试验的小鼠群体，数据起始于首次给药时刻。
f. 总通量（辐射亮度，光子/秒/平方厘米/球面度）变化趋势：数据来源于图5C展示的临床前试验中所有溶剂处理小鼠的颅骨与脊柱区域生物发光成像测量结果。