Regardless of the molecular subtypes, hSCLC demonstrates almost universal inactivating mutations of both tumour suppressor genes TP53 and RB1 (ref. 10), based on which several genetically engineered mouse models (GEMMs) of SCLC have been developed: the PR (Trp53−/− and Rb1−/−)11, PRP130 (Trp53−/−, Rb1−/− and Rbl2−/−)12 and PRPTEN (Trp53−/−, Rb1−/− and Pten−/−)13 models represent the classic SCLC; the PRM model (Trp53−/−, Rb1−/− and MycT58A) recapitulates the variant SCLC14 (Fig. 1a). Here, RB1 is linked to small cell lung carcinoma.