In neuronal cells, the CREB family of transcription factors are the main regulators of brain-derived neurotrophic factor (BDNF) gene expression,399 and emerging evidence suggests that NR4A2 mediates BDNF expression in these cells.400 It is conceivable that a CREB/NR4A2/BDNF signaling pathway activated via PKA or PKD in PDAC cells mediates a positive feedback loop driving pancreatic innervation in the tumor microenvironment and thereby promoting PDAC growth. This evidence concerns the gene CREB1 and neoplasm.