The replication-competent Ad5 of which E1A gene was activated by exogenous transcriptional regulatory sequences, derived from the midkine and survivin genes, achieved cytotoxicity to the pancreatic carcinoma.
This study presents novel MK functions and new upstream signaling effectors that induce its expression to promote PDAC and therefore defines an attractive new therapeutic target in pancreatic cancer.
Here, we have focused our discussion on the latest research, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth factor midkine, which exhibit a wide range of cancer-relevant functions and therefore provide attractive new therapeutic target molecules, in terms of pancreatic cancer and other cancers also.
Notch signaling activated by replication stress-induced expression of midkine drives epithelial-mesenchymal transition and chemoresistance in pancreatic cancer.
From these results, and because it has been reported that AdMKTk and AdCOX-2L Tk in combination with GCV did not reveal significant liver toxicity, we conclude that the MK as well as the COX-2 promoters are promising tumor-specific promoters for Ad vector-based gene therapy of pancreatic cancer.