AUTHOR=Bruno Rossella , Del Re Marzia , Cucchiara Federico , Petrini Iacopo , Alì Greta , Crucitta Stefania , Proietti Agnese , Valleggi Simona , Chella Antonio , Danesi Romano , Fontanini Gabriella 

TITLE=Multiple Resistance Mechanisms to Tyrosine Kinase Inhibitors in EGFR Mutated Lung Adenocarcinoma: A Case Report Harboring EGFR Mutations, MET Amplification, and Squamous Cell Transformation

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.674604

DOI=10.3389/fonc.2021.674604

ISSN=2234-943X

ABSTRACT=<p>Resistance to EGFR tyrosin kinase inhibitors (TKI) inevitably occurs. Here it is reported the case of a young patient affected by lung adenocarcinoma harboring the L858R <italic>EGFR</italic> sensitive mutation. The patient developed multiple TKI resistance mechanisms: T790M <italic>EGFR</italic> resistance mutation, detected only on tumor cell-free DNA, squamous cell transformation and <italic>MET</italic> amplification, both detected on a tumor re-biopsy. The co-occurrence of squamous cell transformation and <italic>de novo MET</italic> amplification is an extremely rare event, and this case confirms how dynamic and heterogeneous can be the temporal and spatial tumor evolution under treatment pressure.</p>