HAND2 and colorectal carcinoma: The CRC components of noradrenergic NB include transcription factors (TFs) ISL1, HAND2, GATA3, PHOX2B, TBX2, and ASCL1, and these TFs form an interconnected autoregulatory feed-forward loop that enforces a malignant noradrenergic phenotype of NB [5, 6, 10–12].