Heterogeneity of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma Harboring Anaplastic Lymphoma Kinase Rearrangements: A Case Report

Lung cancer is a heterogeneous and complex disease that remains the leading cause of cancer-related mortality worldwide. The identification of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangements has changed the treatment of non-small cell lung cancer, creating a personalized treatment era that is based on the appropriate molecular selection of patients. In spite of the efficacy of tyrosine kinase inhibitors (TKIs), acquired resistance remains inevitable due to various mechanisms. The present study reports the case of a 30-year-old patient with stage IV lung adenocarcinoma initially harboring an EGFR mutation. However, following disease progression and a series of treatments, the wild-type EGFR gene was observed and the ALK rearrangements were revealed. Erlotinib administration resulted in a good response in the patient initially, but crizotinib did not. This indicated an association between the secondary mutations in kinases and the drug resistance to TKIs. This case should also highlight the clinical significance of repeat biopsies for the subsequent therapeutic choices at the onset of clinical progression.