Foretinib （GSK1363089）为靶向Met、 RON、Axl、VEGFR的口服多激酶抑制剂。它以较高的亲和力与MET和VEGFR-2 的ATP口袋相结合，竞争性抑制其活性。临床前研究显示，foretinib通过直接影响细胞增殖、抑制肿瘤细胞入侵和血管生成抑制HGF和VEGF受体介导的肿瘤生长。I期临床试验的推荐剂量为240 mg，14天为1个周期，每个周期前5天给药。
一项II期临床研究对foretinib用于乳头状肾细胞癌患者治疗的有效性和安全性及MET通路活性（胚胎或体细胞MET突变）进行评估。结果表明，胚胎MET突变的存在对患者响应具有高度预测性（10例患者中5例存在胚系MET基因突变vs 57 例患者中有5例患者不存在胚系MET基因突变)。Foretinib相关的最常见不良事件为疲劳、高血压、胃肠道毒性以及非致死性肺栓塞。
Last, consistent with our previous preclinical studies, 18 an up-regulation of genes related to cellular adhesion, extracellular matrix disassembly, and angiogenesis, mechanisms of invasion and metastases in METex14 were also up-regulated in our METex14 cohort by pathway analysis. Tumor angiogenesis is hypothesized to promote an immunosuppressive environment 45 and may serve as an additional factor in immunotherapy resistance in METex14. ...
这是为何越来越多医生开始对MET靶向药化疗以及免疫加上抗血管生成药的原因
Molecular dynamic simulations revealed that ensartinib exhibited favorable binding to c-MET. Ensartinib was highly effective in inhibiting the kinase activity of the MET exon 14 deletion protein (IC50 = 7.9 nM). Furthermore, ensartinib potently suppressed the MET pathway and the growth of Hs746T cells that were subcutaneously implanted into mice. Most importantly, of 17 patients with 14 different types of MET exon 14 skipping mutations undergoing ensartinib treatment, 1 (6%) showed a complete response, 11 (65%) achieved a partial response, and 4 (24%) exhibited stable disease. Thus, the objective response rate (ORR) was 71% and the disease control rate (DCR) was 94%, and the ORR in MET-TKI naive patients was even higher (12/15, 80%). In 2 patients with brain metastasis without prior brain radiation, we observed one partial response in the brain, while in the other patient the brain lesions were stable for 6 months. The most frequently reported adverse events were rash, peripheral edema, and nausea; however, no fatal adverse events occurred.
再次看到恩沙替尼
MET inhibition enhances the effect of radiation in MET mutated non-small cell lung cancer brain metastasis patient derived xenograft
简单翻译 脑转移放疗 280别停
吕超 发表于 2022-09-16 06:11
前3后2像不像 ？ NF1？
期待好消息https://majia.yuaigongwu.com/public/emotion/face_075.png
前3后2像不像 ？NF1？
http://oss.yuaigongwu.com/pic/20220916/1663279748889365184.jpg
http://oss.yuaigongwu.com/pic/20220916/1663279748897841348.jpg
http://oss.yuaigongwu.com/pic/20220916/1663279774643162821.jpg
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吕超 发表于 2022-09-15 15:10
新的计划 初探
280+曲美替尼
These results indicate that significant intertumoral heterogeneity exists within the NF1-P53 and NF1 tumorgrafts that promote resistant to MET inhibition. In comparison, NF1-related MPNSTs with high MET expression and activity (i.e. NF1-MET), significant efficacy of MET inhibition was consistently observed。
关键词 NF1-MET，NF1-tp53
吕超 发表于 2022-09-15 15:10
新的计划 初探
280+曲美替尼
NF1基因突变可能导致RAS/RAF/MEK/ERK信号途径失调，而这可能导致细胞以不受控制的方式生长、分裂和复制，并可能导致肿瘤生长。曲美替尼通过抑制这条途径中的MEK酶，潜在地抑制肿瘤生长。
新的计划 初探
280+曲美替尼
http://oss.yuaigongwu.com/pic/20220915/1663225658541243115.jpg
http://oss.yuaigongwu.com/pic/20220915/1663225692249467204.jpg
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http://oss.yuaigongwu.com/pic/20220915/1663225812224512671.jpg
关于MET ，如果克唑替尼有效，因为副作用而不得不换280或赛沃无效的，可以试试ALK药，有时候ALK不一定一次检测出来。