Targeting NPTX1-AMIGO2 to Halt Pancreatic Cancer Metastasis

A recent study published in Cancer Discovery identifies neuronal pentraxin 1 (NPTX1), a secreted neural protein, as a critical driver of metastatic colonization in pancreatic ductal adenocarcinoma (PDAC). Researchers demonstrated that NPTX1 interacts with its receptor, AMIGO2, to promote liver metastasis—the primary metastatic site in PDAC—by stabilizing hypoxia-inducible factor-1α (HIF1α) in the nucleus under hypoxic conditions. Clinical data confirmed elevated NPTX1 levels in human pancreatic tumors and liver metastases. Therapeutically, a high-affinity monoclonal antibody targeting NPTX1 significantly inhibited liver metastasis and primary tumor growth in preclinical models, outperforming standard chemotherapy. These findings position the NPTX1-AMIGO2 axis as a novel therapeutic target, offering a potentially transformative approach for managing metastatic pancreatic cancer.