Investigating the mechanism(s) of anti-Netrin-1 therapy in PDAC
Investigating the mechanism(s) of anti-Netrin-1 therapy in PDAC
There are no available therapeutics that can reverse EMT and reprogram tumors to a more epithelial phenotype. This project will validate this novel mechanism through a pilot clinical trial in which NP137 (the first in human anti-Netrin-1 therapeutic (Netris Pharma) will be given perioperatively in patients with resectable PDAC. The primary endpoint will be an EMT score measured from tumor tissue. Other Aims will examine the mechanism of Unc5b as driver of EMT, strategies to inhibit hepatic stellate cell activation as a means of enhancing efficacy of NP137 and the ability of NP137 to sensitize PDAC to immune checkpoint blockade (ICB).
The Netrin-1 feedforward mechanism that promotes liver metastasis.