Therefore, we speculate that targeting PAICS is primarily effective in WT‐EGFR NSCLC due to two factors: first, EGFR wild‐type NSCLC cells were heavily dependent on the de novo purine synthesis pathway; second, the activation of AKT in EGFR mutant NSCLC cells compensates the blockage of de novo purine synthesis pathway by PAICS silencing. This evidence concerns the gene AKT1 and non-small cell lung carcinoma.