No mutations were identified in mitogen-activated protein kinase kinase 4 (0 of 22), MADH4 (0 of 22), or ACVR1B (0 of 29), making it unlikely that germ-line mutations in these genes account for a significant number of inherited pancreatic cancers.
Our findings support the notion that selective activation of tumor-suppressive MEKK4-MKK4-p38-p21signaling pathway by triptonide is a new approach for pancreatic cancer therapy, providing a new drug candidate for development of novel anti-cancer therapeutics.
Emerging data from a variety of investigators now indicate that overexpression of EphA2, loss of DPC4 and MKK4, and aberrant activation of the Hedgehog signaling pathway are associated with metastatic propensity of pancreatic cancers, providing novel therapeutic targets for the most lethal stage of this disease.