Uncommon and combined EGFR mutations, intratumoral heterogeneity beyond EGFR alterations, drug inefficacy due to adaptive mechanisms exploited by cancer to convey resistance, such as histological transformation of lung adenocarcinoma into small cell lung cancer (SCLC) (37), squamous cell carcinoma (SCC), as well as the activation of alternative pro-oncogenic signaling pathways are also reported (38). This evidence concerns the gene EGFR and lung adenocarcinoma.