A new study highlights the Netrin-1 (NTN1) and Neogenin-1 (NEO1) signaling pathway as a major driver of pancreatic ductal adenocarcinoma (PDAC). Researchers found both proteins are highly overexpressed in tumors, fueled by KRAS mutations and stress signals from nearby nerves. These pathways create a self-reinforcing loop that supports tumor growth and spread.
The research shows this signaling axis plays a dual role in cancer progression. Within tumor cells, NTN1 activates pathways that increase invasion, migration, and stem-like behavior, making the cancer more aggressive and resistant to treatment. At the same time, NTN1 attracts nerve growth into the tumor, where these nerves release signals that further stimulate cancer development.
Targeting this pathway showed promising results in preclinical models. Blocking NTN1 reduced tumor growth, decreased nerve density, and improved survival in mice. It also made tumors more responsive to the immune system by increasing cancer-fighting T cells and reducing immunosuppressive cells, suggesting a potential new treatment strategy for PDAC.