Has programmed cell death ligand-1 MET an accomplice in non-small cell lung cancer?—a narrative review
Recently approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations (e.g., capmatinib, tepotinib) are a new and important therapeutic option for the treatment of non-small cell lung cancer (NSCLC) patients harbouring c-MET alterations. Several experimental studies hav...
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Published in | Translational lung cancer research Vol. 10; no. 6; pp. 2667 - 2682 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
AME Publishing Company
01.06.2021
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Abstract | Recently approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations (e.g., capmatinib, tepotinib) are a new and important therapeutic option for the treatment of non-small cell lung cancer (NSCLC) patients harbouring c-MET alterations. Several experimental studies have provided compelling evidence that c-MET is involved in the regulation of the immune response by up-regulating inhibitory molecules (e.g., PD-L1) and down-regulating of immune stimulators (e.g., CD137, CD252, CD70, etc.). In addition, c-MET was found to be implicated in the regulation of the inflamed tumour microenvironment (TME) and thereby contributing to an increased immune escape of tumour cells from T cell killing. Moreover, it is a major resistance mechanism following treatment of epidermal growth factor receptor mutations (EGFRmut) with tyrosine kinase receptor inhibitors (TKIs). In line with these findings c-MET alterations have also been shown to be associated with a worse clinical outcome and a poorer prognosis in NSCLC patients. However, the underlying mechanisms for these experimental observations are neither fully evaluated nor conclusive, but clearly multifactorial and most likely tumour-specific. In this regard the clinical efficacy of checkpoint inhibitors (CPIs) and TKIs against EGFRmut in NSCLC patients harbouring c-MET alterations is also not yet established, and further research will certainly provide some guidance as to optimally utilise CPIs and c-MET inhibitors in the future. |
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AbstractList | Recently approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations (e.g., capmatinib, tepotinib) are a new and important therapeutic option for the treatment of non-small cell lung cancer (NSCLC) patients harbouring c-MET alterations. Several experimental studies have provided compelling evidence that c-MET is involved in the regulation of the immune response by up-regulating inhibitory molecules (e.g., PD-L1) and down-regulating of immune stimulators (e.g., CD137, CD252, CD70, etc.). In addition, c-MET was found to be implicated in the regulation of the inflamed tumour microenvironment (TME) and thereby contributing to an increased immune escape of tumour cells from T cell killing. Moreover, it is a major resistance mechanism following treatment of epidermal growth factor receptor mutations (EGFRmut) with tyrosine kinase receptor inhibitors (TKIs). In line with these findings c-MET alterations have also been shown to be associated with a worse clinical outcome and a poorer prognosis in NSCLC patients. However, the underlying mechanisms for these experimental observations are neither fully evaluated nor conclusive, but clearly multifactorial and most likely tumour-specific. In this regard the clinical efficacy of checkpoint inhibitors (CPIs) and TKIs against EGFRmut in NSCLC patients harbouring c-MET alterations is also not yet established, and further research will certainly provide some guidance as to optimally utilise CPIs and c-MET inhibitors in the future. |
Author | Dempke, Wolfram C. M. Fenchel, Klaus |
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Copyright | 2021 Translational Lung Cancer Research. All rights reserved. 2021 Translational Lung Cancer Research. |
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Notes | Contributions: (I) Conception and design: Both authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors. |
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Title | Has programmed cell death ligand-1 MET an accomplice in non-small cell lung cancer?—a narrative review |
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