YES1 and MYC Amplifications as Synergistic Resistance Mechanisms to Different Generation ALK Tyrosine Kinase Inhibitors in Advanced NSCLC: Brief Report of Clinical and Preclinical Proofs

Introduction: ALK tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced ALK-positive NSCLC. Nevertheless, drug resistance inevitably occurs. Here, we report a case of a patient with metastatic ALK-positive lung adenocarcinoma with an impressive resistance to sequential treatment with ALK TKIs mediated by YES1 and MYC amplification in a contest of epithelial-to-mesenchymal transition and high progressive chromosomal instability... Conclusions: In conclusion, YES1 and MYC amplifications are candidates to justify a rapid acquired resistance to crizotinib entailing primary brigatinib and lorlatinib resistance. In this context, a combination strategy of ALK TKI with dasatinib could be effective to overcome a rapid resistance. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2022.100278

Authors: Roberta Minari, Samuel Valentini, Denise Madeddu, Andrea Cavazzoni, Silvia La Monica, Costanza Anna Maria Lagrasta, Roberto Bertorelli, Veronica De Sanctis, Paola Fassan, Cinzia Azzoni, Lorena Bottarelli, Caterina Frati, Letizia Gnetti, Francesco Facchinetti, Pier Giorgio Petronini, Roberta Alfieri, Alessandro Romanel, Marcello Tiseo