Acquired Resistance of Non–Small Cell Lung Cancer Cells to MET Kinase Inhibition Is Mediated by a Switch to Epidermal Growth Factor Receptor Dependency
http://cancerres.aacrjournals.org/content/70/4/1625.long
Initial Clinical Sensitivity and Acquired Resistance to MET Inhibition in MET-Mutated Papillary Renal Cell Carcinoma
Jennifer R. Diamond, Ravi Salgia, Marileila Varella-Garcia, Rajani Kanteti, Patricia M. LoRusso, Jeffrey W. Clark, Ling-Guo Xu, Keith Wilner, S. Gail Eckhardt, Keith A. Ching, Maruja E. Lira, Eric F.P.M. Schoenmakers, James G. Christensen, and D. Ross Camidge
JCO Jun 1, 2013:e254-e258; published online on April 22, 2013;
http://www.ncbi.nlm.nih.gov/pubmed/23610116
met-and-kras-amplification-mediate-resistance-to-met-inhibitors
http://pharmastrategyblog.com/2010/09/met-and-kras-amplification-mediate-resistance-to-met-inhibitors.html/
Genome-wide Analysis Suggests that cMET is a Driver of RAS
http://www.ibclifesciences.com/upload/wysiwyg/drug_discovery_series/D10201/Watters_genome-wide_analysis.pdf
马老师你好;什么检测手段能查出T790m突变。这几天一直在寻找方法没找到，在这里求教了。我易已耐药，是不是和T790m突变有关系，不懂，想学习。谢谢！
huanzi 发表于 2013-10-9 17:11 static/image/common/back.gif
马老师你好;什么检测手段能查出T790m突变。这几天一直在寻找方法没找到，在这里求教了。我易已耐药，是不是 ...
谢谢！我做气管镜时，还有白片，我明白了，需要时我会咨询你。
Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
http://www.pnas.org/content/102/21/7665.full
Evaluation of safety and efficacy of tivantinib in the treatment of inoperable or recurrent non-small-cell lung cancer.
http://www.ncbi.nlm.nih.gov/pubmed/23378782
http://europepmc.org/articles/PMC3559079?pdf=render
Breast cancer-derived bone metastasis can be effectively reduced through specific c-MET inhibitor tivantinib (ARQ 197) and shRNA c-MET knockdown.
http://www.ncbi.nlm.nih.gov/pubmed/22027690
Tumoral MET/HGF expression and MET gene amplification in patients with ALK 2p23 fusion driven lung cancer.
http://meetinglibrary.asco.org/content/116773-132
Background: MET receptor and its ligand HGF are both promising targets in non-small cell lung cancer (NSCLC) therapy. Crizotinib, a recently approved ALK inhibitor for NSCLC harboring oncogenic ALK 2p23 fusion (ALK+), was initially developed as a bona fide MET inhibitor. The role of MET/HGF pathway in ALK+ NSCLC is still unknown. Methods: The study included 73 NSCLC patients tested for ALK rearrangements at Cleveland Clinic (2000-2012), including 21 ALK+ and 52 ALK-. Immunohistochemistry (IHC) on FFPE tumor tissue was performed for c-MET using a monoclonal CONFIRM antibody (SP44, Ventana) with Ventana Benchmark XT automated immunostainer and for HGF using a polyclonal antibody (R&D) following a manual protocol. IHC scoring was interpreted on a 4-tier system (0, 1+, 2+, 3+). MET gene amplification by MET/Chromosome 7 dual probe in-situ hybridiazation (DISH) (Ventana) was also performed. Statistical analysis was performed using Fisher exact test in JMP. Results: Of the tested tumors, 61 were adenocarcinoma (21 ALK+ and 40 ALK-), 6 squamous cell, 4 large cell and 2 NSCLC-NOS. None received any MET inhibitor prior to tissue collection. MET expression by IHC score 0-3 was: 35%, 33%, 15% and 17% in ALK-, and 5%, 37%, 42% and 16% in ALK+ tumor group, respectively. HGF IHC score 0-3 was 34%, 55%, 11% and 0% in ALK-, and 0%, 63%, 32% and 5% in ALK+ tumor group, respectively. The percentages of high MET or HGF expression (2+ or 3+) were higher in ALK+ group compared to ALK- (58% vs 32%, p=0.06, and 37% vs 11%, p=0.03). The correlation coefficient between MET and HGF expression was 0.48. MET gene amplification by DISH was detected in 15% (7/47) ALK- tumors but 0% (0/15) ALK+ tumors (difference not statistically significant, p=0.18). The correlation coefficient between MET IHC and MET gene amplification was 0.33. Conclusions: MET and HGF expression is commonly seen in NSCLC, with more frequent high expression levels in ALK+ than ALK- tumors. Using a newly developed DISH method, we show that MET gene amplification tend to be less frequent in ALK+ tumor. A prospective study with larger sample size is warranted to further define the role of MET/HGF as biomarkers in the biology of NSCLC with ALK rearrangements and their targeted therapy.
Co-overexpression of Met and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells.
http://www.ncbi.nlm.nih.gov/pubmed/20019837
http://www.neoplasia.com/pdf/manuscript/v11i12/neo09622.pdf