Two models for the transformation of normal human cells to NE tumors are outlined. Chen et al. (2019) started with cultures of hESCs, converted them into pulmonary NE cells, and then sequentially inactivated the Notch pathway, RB1 and TP53. The resultant cells and tumors derived from the inoculation of the cells into immunosuppressed mice closely resembled SCLC cells and tumors respectively, both morphologically and genetically. Park et al. (2018) started with cultures derived from either human bronchial epithelial cells or adult prostate tissues. From the prostate cells, they isolated basal cells, the precursors of the prostatic epithelium. They used lentiviral transduction to perform five genetic manipulations, inhibition of RB1 and TP53, and up-regulation of MYC, AKT, and BCL2. The transduced cells were grown as organoid cultures and subsequently inoculated into immunosuppressed mice. The resultant tumors closely resembled either SCLC (from bronchial epithelial cells) or small cell prostate cancers (from prostate cultures), both morphologically and genetically.