MET: A New Promising Biomarker in Non-Small-Cell Lung Carcinoma

Pérez-Ramírez, Cristina; Cañadas-Garre, Marisa; Jiménez-Varo, Enrique; Faus-Dáder, María José; Calleja‐Hernández, Miguel Ángel

doi:10.2217/pgs.15.11

Cited by 21 publications

(16 citation statements)

References 159 publications

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“…16,17 Identifying MET amplification in patients with lung cancer could aid the development of personalized medicine by identifying those patients who will benefit from treatment with MET inhibitors. Furthermore, we also did not detect the four cases of MET amplification in cfDNA that were found by NGS using tDNA.…”

Section: Concordance Between Tumor and Plasma Resultssupporting

confidence: 72%

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer

Liu

Liu²,

Шао

et al. 2018

Genes Chromosomes & Cancer

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Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors. In this study, we developed a next-generation sequencing (NGS)-based test for the detection of clinically relevant mutations in ctDNA and evaluated the feasibility of using this ctDNA NGS-based assay as an alternative to tissue genotyping. Tissue and matched blood samples were obtained from 72 patients with advanced nonsmall cell lung cancer (NSCLC). NGS-based testing was performed using plasma cell-free DNA (cfDNA) samples of all 72 patients as well as tumor DNA samples of 46 patients. Of the remaining 26 patients, tDNA was tested by amplification refractory mutation system PCR (ARMS-PCR) because of insufficient tissue sample or quality for NGS. Of the 46 patients who had tDNA and cfDNA NGS performed, we found 20 patients were concordant between tDNA and ctDNA alterations and 21 sample pairs were discordant because of additional alterations found in tDNA. Considering all clinically relevant alterations, the concordance rate between tDNA and ctDNA alterations was 54.9% with a sensitivity of 53.2% and a specificity of 75.0%. Our findings demonstrate that targeted NGS using cfDNA is a feasible approach for rapid and accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.

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Section: Concordance Between Tumor and Plasma Resultssupporting

confidence: 72%

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer

Liu

Liu²,

Шао

et al. 2018

Genes Chromosomes & Cancer

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“…More recently, oncogenic splice-site mutations of MET at exon 14 have been discovered and were shown to activate c-MET in patients with NSCLC and SCLC [115–118]. In terms of treatment, MET -directed anti-cancer therapies are currently under preclinical and clinical trials and include c-MET inhibitors (Tivantinib, Cabozantinib and Foretinib), anti-MET antibodies (Onartuzumab), and anti-HGF (as the hepatocyte growth factor is a MET ligand) antibodies (Rilotumumab and Ficlatuzumab) [119]. Furthermore, crizotinib is a dual ALK/MET inhibitor, presently approved for the treatment of NSCLC patients harboring an EML4-ALK fusion.…”

Section: Genetic Analysismentioning

confidence: 99%

“…Furthermore, crizotinib is a dual ALK/MET inhibitor, presently approved for the treatment of NSCLC patients harboring an EML4-ALK fusion. Its efficacy has also been reported in some cases of MET amplification, suggesting its potential interest in MET -targeted therapies [119]. …”

Section: Genetic Analysismentioning

confidence: 99%

Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer

et al. 2016

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Personalized medicine has emerged as the future of cancer care to ensure that patients receive individualized treatment specific to their needs. In order to provide such care, molecular techniques that enable oncologists to diagnose, treat, and monitor tumors are necessary. In the field of lung cancer, cell free DNA (cfDNA) shows great potential as a less invasive liquid biopsy technique, and next-generation sequencing (NGS) is a promising tool for analysis of tumor mutations. In this review, we outline the evolution of cfDNA and NGS and discuss the progress of using them in a clinical setting for patients with lung cancer. We also present an analysis of the role of cfDNA as a liquid biopsy technique and NGS as an analytical tool in studying EGFR and MET, two frequently mutated genes in lung cancer. Ultimately, we hope that using cfDNA and NGS for cancer diagnosis and treatment will become standard for patients with lung cancer and across the field of oncology.

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“…The most common type of lung cancer is nonsmall cell lung cancer (NSCLC), which accounts for 80% of lung cancers and presents different subtypes: squamous cell, carcinoma, adenocarcinoma, and large cell carcinoma [1][2][3]. The most common type of lung cancer is nonsmall cell lung cancer (NSCLC), which accounts for 80% of lung cancers and presents different subtypes: squamous cell, carcinoma, adenocarcinoma, and large cell carcinoma [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Tigecycline targets nonsmall cell lung cancer through inhibition of mitochondrial function

Jia

Chen

et al. 2016

Fundamemntal Clinical Pharma

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Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains therapeutically a challenge. A strategy to target NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. We show that tigecycline, an FDA-approved antibiotic drug, preferentially targets NSCLC cells. Tigecycline is effective in inhibiting proliferation and inducing apoptosis of multiple cell lines derived from two common NSCLC subtypes: adenocarcinoma and squamous cell carcinoma. Tigecycline also dose-dependently inhibits colony formation of NSCLC subpopulation of cells with highly proliferative and invasive properties. Compared to NSCLC cells, tigecycline affects proliferation and survival of normal fibroblast cells significantly to a less extent. More importantly, tigecycline significantly inhibits NSCLC tumor growth through decreasing proliferation and increasing apoptosis of tumor cells in vivo. Tigecycline significantly inhibits mitochondrial respiration, mitochondrial membrane potential, and ATP levels and increases reactive oxygen species (ROS), suggesting that tigecycline impairs mitochondrial functions. Our study suggests that tigecycline may be a useful therapeutic agent, and inhibiting mitochondrial functions may represent a new targeted therapy for NSCLC.

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MET: A New Promising Biomarker in Non-Small-Cell Lung Carcinoma

Cited by 21 publications

References 159 publications

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer

Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer

Tigecycline targets nonsmall cell lung cancer through inhibition of mitochondrial function

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