Squamous cell carcinoma differentiation at progression as a resistance mechanism in metastatic non-small cell lung carcinoma harbouring a targetable mutation

Non-small cell lung cancer (NSCLC) comprises approximately 85% of patients diagnosed with metastatic disease,1 of which the major histological subtypes are adenocarcinoma (ADC) and squamous cell carcinoma (SCC).2 These tumour types are thought to originate from different cell types, typically arise in different locations within the lung, express differing molecular alteration profiles and are variably associated with tobacco exposure. Lung ADC are thought to arise from alveolar type II cells, bronchoalveolar stem cells, or club cells,3 are more often located distally, and have been identified to harbour a variety of therapeutically targetable oncogenic molecular alterations involving genes such as EGFR, ALK, ROS1, RET, BRAF, MET, NTRK, TP53 and HER2.