GEMMs of SCLC overexpressing the intracellular domain of NOTCH1 develop neuroendocrine-low tumors from primary neuroendocrine-high tumors, and NOTCH pathway-mediated RE1 silencing transcription factor (Rest) and hes family bHLH transcription factor 1 (Hes1) expression represses neuroendocrine differentiation [20,21]. The gene discussed is HES1; the disease is small cell lung carcinoma.