<i>MET</i> gene fusions in non-small cell lung cancer (NSCLC) in the Chinese population: A multicenter study.

Wang, Wen xian; Xu, C.; Chen, Yu; Zhu, You‐cai; Liu, Yueping; Wang, Hong; Zhuang, Wei; Chen, Xiaohui; Huang, Yun-jian; Lai, Jinhuo; Fang, M.; Zhang, Zhenghua; Tao, Ye; Xu, Shuguang; Xue, Qingwu; Zhao, Hongyu; Cai, Shangli; Chen, Gang; Lv, Tangfeng; Song, Yong

doi:10.1200/jco.2018.36.15_suppl.e13539

Cited by 8 publications

(6 citation statements)

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“…FGFR fusions were identified in approximately 0.2% of NSCLC cases from a large series of 26,054 patients and included one patient that had clinical benefit to an investigational FGFR inhibitor [90]. Similarly, low frequencies have been identified for BRAF fusions (0.2-2.8%) [91,92], MET fusions (0.04%) [93], and EGFR fusions (0.08%) [94]. Owing to the rarity of these fusion drivers and the limited epidemiological and clinical characterization of these cohorts, our understanding of the incidence of BM and intracranial efficacy of targeted therapies is limited.…”

Section: Other Rare Fusions In Nsclcmentioning

confidence: 99%

Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers

Tan

Itchins

Khasraw

2020

IJMS

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The management of non-small cell lung cancer (NSCLC) has transformed with the discovery of therapeutically tractable oncogenic drivers. In addition to activating driver mutations, gene fusions or rearrangements form a unique sub-class, with anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) targeted agents approved as the standard of care in the first-line setting for advanced disease. There are a number of emerging fusion drivers, however, including neurotrophin kinase (NTRK), rearrangement during transfection (RET), and neuregulin 1 (NRG1) for which there are evolving high-impact systemic treatment options. Brain metastases are highly prevalent in NSCLC patients, with molecularly selected populations such as epidermal growth factor receptor (EGFR) mutant and ALK-rearranged tumors particularly brain tropic. Accordingly, there exists a substantial body of research pertaining to the understanding of brain metastases in such populations. Little is known, however, on the molecular mechanisms of brain metastases in those with other targetable fusion drivers in NSCLC. This review encompasses key areas including the biological underpinnings of brain metastases in fusion-driven lung cancers, the intracranial efficacy of novel systemic therapies, and future directions required to optimize the control and prevention of brain metastases.

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Section: Other Rare Fusions In Nsclcmentioning

confidence: 99%

Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers

Tan

Itchins

Khasraw

2020

IJMS

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“…Anti-MET antibody-drug conjugates are a more recent approach; telisotuzumab vedotin, an anti-MET antibody conjugated with monomethyl auristatin E (a tubulin polymerization inhibitor), has shown favorable antitumor activity in patients with NSCLC and MET overexpression in a phase I study and is being investigated in a phase II trial (NCT03539536) [5][6][7]. MET TKIs have been investigated in patients with NSCLC harboring MET overexpression, MET amplification, or MET exon 14 skipping; case reports have reported activity in NSCLC with MET fusions [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The promise of selective MET inhibitors in non-small cell lung cancer with MET exon 14 skipping

Salgia

Sattler

Scheele

et al. 2020

Cancer Treatment Reviews

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Dysregulated activation of the MET tyrosine kinase receptor is implicated in the development of solid tumors and can arise through several mechanisms, including gene amplification, overexpression of the receptor and/or its ligand hepatocyte growth factor (HGF), and the acquisition of activating mutations. The most common activating mutations cause exon 14 to be skipped during MET mRNA splicing. This in-frame deletion, known as MET exon 14, results in production of a shortened receptor that lacks a juxtamembrane domain but retains affinity for HGF. However, the negative regulatory function located within this protein sequence is lost, leading to receptor accumulation on the cell surface and prolonged activation by HGF. MET mutations causing exon 14 skipping appear to be true oncogenic drivers and occur in patients and tumors with distinct characteristics.Increasing evidence suggests that tumors carrying such mutations are sensitive to MET inhibition, raising the hope that selective MET inhibitors will provide patients with optimal anticancer activity with minimal toxicity.We discuss the prospects for selective MET inhibitors in the treatment of non-small cell lung cancer harboring MET exon 14 skipping.

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“…Based on a series of 2410 NSCLC patients, that rate was 0.04% (one patient with MET-ATXN7L1 (ataxin-7-like protein-1) fusion). 54…”

Section: Rearrangementsmentioning

confidence: 99%

<p>Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date</p>

Bylicki¹,

Paleiron²,

Assié³

et al. 2020

OTT

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The c-MET proto-oncogene (MET) plays an important role in lung oncogenesis, affecting cancer-cell survival, growth and invasiveness. The MET receptor in non-small-cell lung cancer (NSCLC) is a potential therapeutic target. The development of high-output nextgeneration sequencing techniques has enabled better identification of anomalies in the MET pathway, like the MET exon-14 (METex14) mutation. Moreover, analyses of epidermal growth factor-receptor (EGFR) and mechanisms of resistance to tyrosine-kinase inhibitors (TKIs) demonstrated the importance of MET amplification as an escape mechanism in patients with TKI-treated EGFR-mutated NSCLCs. This review summarizes the laboratory findings on MET and its anomalies, trial results on METex14 alterations and MET amplification in non-EGFR mutated NSCLCs, and acquired resistance to TKI in EGFR-mutated NSCLCs. The outcomes of the first trials with anti-MET agents on non-selected NSCLC patients or those selected for MET overexpression were disappointing. Two situations seem the most promising today for the use of anti-MET agents to treat these patients: tumors harboring METex14 and those EGFR-sensitive mutation mutated under TKI-EGFR with a MET-amplification mechanism of resistance or EGFR-resistance mutation.

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MET gene fusions in non-small cell lung cancer (NSCLC) in the Chinese population: A multicenter study.

Cited by 8 publications

References 0 publications

Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers

Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers

The promise of selective MET inhibitors in non-small cell lung cancer with MET exon 14 skipping

<p>Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date</p>

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