Hedgehog signaling pathway as a new therapeutic target in pancreatic cancer

Figure 1 Schematic review. Hedgehog (Hh) signaling is activated in both autocrine and paracrine pathways. Tumor associated stroma cells play a pivotal role in tumor progression related to activation of Hh signaling [paracrine pathways (1) and (2)]. Induction of sonic Hh (Shh) is closely associated with activation of the nuclear factor kappa-light-chain-enhancer of activated B cells transcription factor in pancreatic cancer. Shh is produced by NF-κB activation in pancreatic cancer cells and tumor associated stroma cells. Pathways contributing to Smo and Gli1 activation include SDF-1/CXCR4, hypoxia, KRAS and MAP3K. The effects of Hh inhibitors including GDC-0449 (vismodegib), LDE225 (erismodegib), IPI-926 (saridegib), BMS-663513 and GANT-61 in clinical trials are under investigation. Dotted arrows show components of the Hh signaling pathway in tumor cells focused on in this review.