PIK3CA and small cell carcinoma: EGFR-dependent mechanisms due to additional EGFR mutations, such as C797S, L792X, and L718X, have been reported to be involved in osimertinib resistance, along with multiple EGFR-independent mechanisms, including MET amplification, HER2 amplification, gene reconstitution, PIK3CA mutation, mitogen-activated protein kinase (MAPK) signaling activation, small cell carcinoma transformation, and epithelial-mesenchymal transition [17].