Recent studies have revealed several molecular mechanisms underlying EGFR-TKI resistance, including a second mutation at T790 M in exon 20 of EGFR, activation of alternative receptor tyrosine kinases (RTKs) or PI3K signaling, small-cell lung cancer (SCLC) transformation, and epithelial-mesenchymal transition (EMT) [8–10]. The gene discussed is PIK3CA; the disease is small cell lung carcinoma.