Recent SCLC profiling studies on cancer cell lines, PDXs, GEMMs, and primary human tumors suggest a model of distinct subtypes defined by the relative expression of four key transcriptional regulators: achaete-scute homolog 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NEUROD1), yes-associated protein 1 (YAP1), and POU class 2 homeobox 3 (POU2F3).33 The gene discussed is ASCL1; the disease is cancer.