PIK3CA and small cell lung carcinoma: In most NSCLC patient cases, the first-line treatment of EGFR-TKIs lose their therapeutic activity within 13 months due to acquired resistance, which is mediated by EGFR target alterations, such as the secondary EGFR (T790M) mutation, by activation of bypass signaling, such as HER2 amplification, MET amplification, PIK3CA, MAPK, BRAF, and multiple signaling pathways, or by phenotypic changes, such as SCLC transformation and the EMT (for review, [56,57]).