Significance of genetic sequencing in patients with lung adenocarcinoma with transformation to small cell lung cancer: a case report and systematic review

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) exhibit a beneficial therapeutic effect on non-small cell lung cancer (NSCLC). However, almost all patients with EGFR-mutant lung cancer develop drug resistance to these agents. Common drug resistance mechanisms include the T790M mutation, c-MET amplification, KRAS mutation, BIM polymorphism deletion and PIK3CA gene mutations. Some NSCLC exhibit transformation into small cell lung cancer (SCLC). A patient case of a 56-year-old man with lung adenocarcinoma (with symptoms of a cough and expectoration that had lasted 1 month) who exhibited an EGFR mutation (19-Del) and was treated with EGFR-TKIs is reported, which transformed into SCLC after failed to targeted therapy. Pathological examination and genome sequencing were carried out when every time the disease progressed, we obtained more comprehensive information and could keep track of the patient’s progress. So, we could adjust the treatment plan at any time according to the results of pathological examination and gene detection. We can get some implications: (I) patients with EGFR mutant lung adenocarcinoma with the double inactivation of RB1 and TP53 genes exhibit an increased risk of SCLC transformation; (II) after SCLC transformation, therapeutic strategies should be adequately adjusted, when SCLC was controlled by chemotherapy the targeted therapy should be considered for the treatment of adenocarcinoma; (III) evidence of the benefits of immunotherapy in patients with SCLC transformation is insufficient; (IV) the achievement of the SCLC phenotype is a late phenomenon during TKI therapy and the prognosis of patients after SCLC diagnosis is poor.