Multiple studies have found that mutations in RB1 and TP53 are closely related to the transformation from lung adenocarcinoma to small cell lung cancer, which often occurs in patients receiving TKIs therapy and is associated with a relatively poor prognosis (27, 28), suggesting that TKIs therapy might not be a good choice for lung cancer patients with COPD. This evidence concerns the gene RB1 and lung adenocarcinoma.