A new study has identified Prolyl 3-hydroxylase 1 (P3H1) as an important driver of pancreatic ductal adenocarcinoma (PDAC) and a potential new treatment target.
Researchers found that P3H1 is highly expressed in both human and mouse pancreatic tumors. Patients with higher P3H1 levels tended to have more advanced disease and shorter disease-free survival. In mouse models, removing the P3H1 gene reduced tumor size and weight and extended median survival by about 20%.
The study also showed that P3H1 plays a key role in shaping the tumor immune environment. When P3H1 was absent, tumors had fewer M2-like tumor-associated macrophages, immune cells that normally support cancer growth and suppress anti-tumor immunity.
Further analysis revealed that P3H1 promotes cancer growth through a pathway involving the proteins PLK1 and β-catenin. This signaling activates genes that drive cell proliferation and release cytokines that attract immune-suppressive macrophages to the tumor.
The findings also suggest therapeutic potential. In laboratory models and patient-derived organoids, combining a PLK1 inhibitor with standard chemotherapy drugs such as gemcitabine and nab-paclitaxel produced stronger tumor-killing effects than chemotherapy alone.
Researchers say targeting the P3H1 pathway could both slow tumor growth and make pancreatic tumors more responsive to existing treatments.