Epithelial Mesenchymal Transition in Lung Adenocarcinoma MET Exon 14 Skipping Mutation Driven Fully Responder to TKI Inhibitor

Caterina Chiappetta*, Ettore D’argento, Angelo Minucci, Raffaella Carletti, Antonio Vitale, Paolo Graziano

AOU Policlinico Umberto I, Sapienza University of Rome, Italy Comprehensive Cancer Center, Department of Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Laboratory of Clinical Molecular and Personalized Diagnostics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Department of Radiological, Oncological and Pathological Sciences, University of Rome, Italy

^*Correspondance to: Caterina Chiappetta 

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Abstract:

Epithelial-to-mesenchymal transition (EMT) represents a rare but aggressive transformation in non-small cell lung cancer (NSCLC), often associated with resistance to therapy. We report a case of EMT in a 47-year-old non-smoker with MET exon 14 skipping mutation-driven lung adenocarcinoma, who developed a gingival metastasis after immune checkpoint inhibitor (ICI) treatment. Histologic and molecular analyses confirmed EMT features and the persistence of MET exon 14 skipping in the oral lesion. Capmatinib treatment led to rapid clinical response, though disease progression occurred after five months. Subsequent metastases revealed a new PTCH1 splice site alteration, suggesting EMT promotion via Hedgehog pathway activation. This case highlights EMT as a mechanism of resistance post-ICI and underscores the importance of comprehensive molecular profiling. EMT presents diagnostic and therapeutic challenges, requiring dynamic, personalized approaches to optimize care and address evolving resistance in advanced NSCLC.

Keywords:

TKI Inhibitor

Cite the Article:

Chiappetta C, D’argento E, Minucci A, Carletti R, Vitale A, Graziano P. Epithelial Mesenchymal Transition in Lung Adenocarcinoma MET Exon 14 Skipping Mutation Driven Fully Responder to TKI Inhibitor. Ann Clin Case Rep. 2025; 10: 2771..