High MET Gene Copy Number Leads to Shorter Survival in Patients with Non-small Cell Lung Cancer

Go, Heounjeong; Jeon, Yoon Kyung; Park, Hyojin; Sung, Sook-Whan; Seo, Jeong‐Wook; Chung, Doo Hyun

doi:10.1097/jto.0b013e3181ce3d1d

Cited by 193 publications

(156 citation statements)

References 33 publications

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“…21,46,55,56). Interestingly, a much greater incidence of MET amplification, ranging from 5% to 22%, has been reported in patients with NSCLC following treatment with erlotinib/gefitinib (Table 1; refs.…”

Section: Met Amplificationmentioning

confidence: 99%

“…Amplification of MET (and overexpression of the protein) is also a common event in brain metastases of NSCLC (59). Furthermore, fluorescence in situ hybridization (FISH)-positive MET status predicts worse survival in patients with advanced NSCLC (56,60). An analysis of OS based on MET FISH status-derived GCN revealed that increased GCN is an independent negative prognostic factor in surgically resected NSCLC, with OS of 25.8 months for patients with MET !5 copies/cell compared with 47.5 months for patients with MET <5 copies/cell (P ¼ 0.0045; ref.…”

Section: Met Amplificationmentioning

confidence: 99%

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MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

Salgia

2017

Molecular Cancer Therapeutics

133

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MET or hepatocyte growth factor (HGF) receptor pathway signaling mediates wound healing and hepatic regeneration, with pivotal roles in embryonic, neuronal, and muscle development. However, dysregulation of MET signaling mediates proliferation, apoptosis, and migration and is implicated in a number of malignancies. In non-small cell lung cancer (NSCLC), aberrant MET signaling can occur through a number of mechanisms that collectively represent a significant proportion of patients. These include MET or HGF protein overexpression, MET gene amplification, MET gene mutation or fusion/rearrangement, or aberrations in downstream signaling or regulatory components. Responses to MET tyrosine kinase inhibitors have been documented in clinical trials in patients with MET-amplified or METoverexpressing NSCLC, and case studies or case series have shown that MET mutation/deletion is a biomarker that is also predictive of response to these agents. However, other recent clinical data have highlighted an urgent need to elucidate optimal biomarkers based on genetic and/or protein diagnostics to correctly identify patients most likely to benefit in ongoing clinical trials of an array of MET-targeted therapies of differing class. The latest advances in the development of MET biomarkers in NSCLC have been reviewed, toward establishing appropriate MET biomarker selection based on a scientific rationale. Mol Cancer Ther; 16(4); 555-65.Ó2017 AACR.

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Section: Met Amplificationmentioning

confidence: 99%

Section: Met Amplificationmentioning

confidence: 99%

MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

Salgia

2017

Molecular Cancer Therapeutics

133

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“…MET gene copy number was estimated using an LSI MET SpectrumRed/CEP7 SpectrumGreen probe (Abbott Molecular) and interpreted using the above University of Colorado Cancer Center system or Cappuzzo criteria (high MET gene copy number; mean ≥ 5 copies per cell) as described previously. 30 …”

Section: Patients and Samplesmentioning

confidence: 99%

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

et al. 2015

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Immunotherapies targeting the programmed cell death-1/programmed cell death-ligand 1 pathway have emerged as promising therapeutic strategies for lung cancer. However, the expression pattern and prognostic implications of programmed cell death-ligand 1 and 2 and programmed cell death-1 in comparison with the histology and genetic alterations in pulmonary adenocarcinomas remains unclear and thus were addressed here. Programmed cell death-ligand 1 and 2 expression in tumor cells and the quantities of programmed cell death-1 + and CD8 + tumor-infiltrating lymphocytes were immunohistochemically evaluated in 497 resected pulmonary adenocarcinomas and analyzed according to clinicopathological and genetic statuses. Programmed cell death-ligand 1 and 2 expression were observed in 59% and 64% of pulmonary adenocarcinomas, respectively, and showed a strong positive correlation with each other (Po 0.001). Programmed cell death-ligand 1 expression was higher in nodal metastasis cases (P = 0.006), smokers (P = 0.056), poorly differentiated tumors and histologic subtypes of solid and micropapillary patterns (Po0.001). There was no significant difference in programmed cell death-ligand 1 and 2 expression according to EGFR mutation status. However, programmed cell death-ligand 1 expression was correlated with ALK translocation (P = 0.054) and expression of EGFR and MET (Po 0.001). Meanwhile, programmed cell death-ligand 2 expression was correlated with ALK translocation (P = 0.052), and expression of MET (Po 0.001) and ERBB2 (P = 0.013). The numbers of CD8 + and programmed cell death-1 + lymphocytes were higher in smokers (P = 0.012 and 0.016) and MET-expressing adenocarcinomas (Po 0.001). Patients expressing programmed cell death-ligand 1 and/or high ratios of programmed cell death-1 + /CD8 + lymphocytes showed shorter disease-free survival (P = 0.001). Our study demonstrated that programmed cell death-ligand 1 and 2 expression varied with histology, EGFR, ALK, MET, and ERBB2 statuses, and activation of the programmed cell death-1/programmed cell death-ligand 1 pathway may be a poor prognostic factor in pulmonary adenocarcinomas.

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“…The two most commonly used criteria are the University of Colorado Cancer Center Criteria (UICC; ref. 50 ) and the Cappuzzo scoring system ( 51 ). Both of these scoring systems, however, evaluate aneuploidy and real MET amplifi cation at the same time.…”

Section: A General Problem: Defi Nition Of Met Amplifi Cationmentioning

confidence: 99%

Cell-Autonomous and Non–Cell-Autonomous Mechanisms of HGF/MET–Driven Resistance to Targeted Therapies: From Basic Research to a Clinical Perspective

Corso

Giordano

2013

Cancer Discovery

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Targeted therapies have opened new perspectives in clinical oncology. However, clinicians have observed a lack of response in a relevant percentage of patients and frequent relapse in patients who initially respond. Therefore, a compelling challenge is to identify mechanisms underlying resistance and strategies to circumvent these hurdles. A growing body of evidence indicates that MET, the tyrosine kinase receptor for hepatocyte growth factor (HGF), is frequently implicated in resistance to targeted therapies. In this review, we highlight cell-autonomous and non-cell-autonomous mechanisms through which MET drives resistance, and we discuss some unsolved issues related to the selection of patients who could benefi t from combined therapies. Signifi cance:Resistance is, at present, the major limitation to the effi cacy of targeted therapies. Inappropriate MET activation is very frequently implicated in the onset of primary and secondary resistance to these therapies. Deciphering the role of the HGF/MET axis in resistance to different drugs could guide the design of new clinical trials based on combinatorial therapies, and it might help to overcome, or possibly prevent, the onset of resistance. Cancer Discov; 3(9);

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High MET Gene Copy Number Leads to Shorter Survival in Patients with Non-small Cell Lung Cancer

Abstract: Our results suggest that increased MET GCN would be an independent poor prognostic factor in SCC of the lung.

Cited by 193 publications

References 33 publications

MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

Cell-Autonomous and Non–Cell-Autonomous Mechanisms of HGF/MET–Driven Resistance to Targeted Therapies: From Basic Research to a Clinical Perspective

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