Has programmed cell death ligand-1 MET an accomplice in non-small cell lung cancer?-a narrative review

Dempke, Wolfram C. M. und Fenchel, Klaus (2021): Has programmed cell death ligand-1 MET an accomplice in non-small cell lung cancer?-a narrative review. In: Translational Lung Cancer Research, Bd. 10, Nr. 6: S. 2667-2682

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2218-6751
• Sprache: Englisch