难缠的L1195V
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Recondo et al. reported a patient harboring MET exon 14 skipping who experienced PD on crizotinib, and a resistance MET mutation of Y1230C was detected both in plasma and tumor tissue at the time of progression. This patient had a PR after switched to merestinib.55 These results supported that merestinib may provide a therapeutic option to patients with METex14. The first-in-human phase I study was to evaluate the safety and tolerability of merestinib including three types of tumor without NSCLC. Overall, 60 (32%) of the 186 patients enrolled in the study had a best response of SD, and recommended a dosing of merestinib at 120 mg once daily based on acceptable exposure and safety.56 A phase II study conducted by Awad et al. was to evaluate the safety and efficacy of merestinib in patients with advanced METex14 NSCLC or patients with advanced cancer with NTRK rearrangements (NCT02920996).54
Glesatinib Glesatinib (MGCD265; Mirati Therapeutics) is another orally bioavailable, type II, multi-targeted inhibitor with potential anti-tumor activity. Glesatinib binds to and inhibits the phosphorylation of several RTKs, including the MET receptor, the TEK/TIE-2 receptor, RON, SMO, and VEGFR types 1, 2, and 3. Preclinical studies showed that glesatinib resulted in a dose-dependent inhibition of cancer cell growth with an IC50 value of 80 nM on NSCLC H1299 cells.57 A patient with METex14 NSCLC showed response to glesatinib after relapsing to crizotinib, including a reduction in size of a MET Y1230H mutation-positive liver metastases and concurrent loss of detection of this mutation in plasma DNA.
关于MET与D-2聚体的关系，一旦耐药D2聚体飙升，这是大部分MET的特点。
是D2高了引起转移，还是肿瘤转移引起D2高，还是相辅相成。
把D-2牢牢控制在标准以下是否会延缓肿瘤转移值得观察。
MET融合重排 也是一种MET耐药继发突变，甚至是ALK EGFR耐药突变，比例很低，群友中有用克唑替尼有效的，280比较难。
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记录一段 MET 遇到的故事
http://oss.yuaigongwu.com/video/20220609/1654779767507536150.mp4
这是MET14 跳突免疫的效果，观察发现 MET14 供体端效果比受体短效果更好，样本少。
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一张迟到的MET扩增报告，FISH是金标准。 MET初期不控制，一旦做大就很难了。
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非常好的图，磨玻璃结节 混合磨玻璃 实性结节
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对于MET扩增 一般小基因公司不一定测出来，大的基因公司几率高一些，FISH更可靠。
EGFR扩增和MET或MET14扩增原发双突变，一定要早上METTKI，如果开始没测出来，后期发现METTKI的效果大大减小。