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| Item Type: | Article |
|---|---|
| Title: | Liquid biopsy-based detection of acquired MET resistance enables sequential targeted therapy in MET fusionpositive NSCLC |
| Creators Name: | Rosnev, Stanislav, Klein, Katharina, Heukamp, Lukas, Lenk, Julian, Joosten, Maria, Möbs, Markus, Grob, Tobias, Benary, Manuela, Vecchione, Loredana, Ott, Claus-Eric, Modest, Dominik P., Knödler, Maren, Keller, Ulrich, Frost, Nikolaj, Keilholz, Ulrich, Kiewe, Philipp and Rieke, Damian T. |
| Abstract: | Oncogenic alterations in MET represent therapeutically actionable driver alterations in non-small cell lung cancers (NSCLC). Among these, MET fusions are rare, occurring in approximately 0.1-0.3% of NSCLC. We report the case of a 52-year-old woman with metastatic, TTF1-positive lung adenocarcinoma harboring a KIF5B::MET fusion. After progression on chemotherapy and immunotherapy, she achieved a durable response lasting nearly five years on third-line treatment with the type Ia MET inhibitor crizotinib. At the time of suspected disease progression, two tissue re-biopsies were non-diagnostic due of insufficient tumor cell content. Circulating tumor DNA (ctDNA) analysis identified two newly acquired on-target resistance mutations within the MET kinase domain (L1213V and Y1248C) in addition to the known KIF5B::MET fusion. After re-evaluation by the institutional molecular tumor board, both alterations were considered mediators of resistance to type I MET inhibitors, with available data indicating preserved sensitivity to type II inhibitors. Based on these findings, the patient was switched to cabozantinib, a multikinase type II MET inhibitor, resulting in a radiographic disease stabilization accompanied by a marked decline in tumor marker levels. This case illustrates the clinical utility of liquid biopsy for molecular resistance monitoring, particularly when tissue re-biopsy is not feasible, supports its integration into clinical decision-making, and underscores the therapeutic relevance of MET inhibitor class-switch strategies in MET fusion-positive disease. |
| Source: | Oncologist |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Page Range: | oyag151 |
| Date: | 21 April 2026 |
| Official Publication: | https://doi.org/10.1093/oncolo/oyag151 |
| PubMed: | View item in PubMed |
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