New Insights into the Driving Mechanism Behind Pancreatic Cancer Metastasis

Research led by Cornell University has uncovered a critical mechanism that facilitates the spread of pancreatic ductal adenocarcinoma, a highly lethal cancer with a five-year survival rate below 10%. Despite its dense fibrotic microenvironment, which should theoretically hinder tumor dissemination and drug delivery, pancreatic cancer often metastasizes efficiently. The study reveals that the receptor ALK7 plays a pivotal role by activating two interconnected pathways: one enhances the mobility of cancer cells through epithelial-mesenchymal transition (EMT), while the other produces enzymes that degrade blood vessel walls, enabling invasion and intravasation.

According to Esak Lee, lead author and assistant professor at Cornell Engineering, ALK7 effectively grants cancer cells both the propulsion to migrate and the tools to invade surrounding tissues. This discovery clarifies previous conflicting findings about ALK7's role, which was previously associated with both promoting and inhibiting metastasis. Using innovative mouse models and advanced organ-on-chip systems that mimic human blood vessels, the researchers demonstrated that inhibiting ALK7 significantly reduces metastasis.

The organ-on-chip platform, developed in Lee's lab, provides a superior model to animal studies for examining cancer invasion and the microenvironment's dynamics. Their experiments showed that when ALK7 activity is blocked, cancer cells cannot invade blood vessels. However, once cancer progresses to a stage where cells circulate in the bloodstream, metastasis occurs rapidly. This highlights the importance of early intervention targeting ALK7 to improve patient outcomes.

The findings suggest that early therapeutic targeting of ALK7 could prevent cancer cells from entering the bloodstream and spreading to other organs such as lungs or liver. Furthermore, this research opens new avenues for studying other cancers and immune cell interactions within the vascular microenvironment, offering promising potential for developing targeted treatments against metastasis.

This study, published in Molecular Cancer (2025), emphasizes the importance of understanding the timing of intervention and presents a new understanding of pancreatic cancer metastasis mechanisms. Source: https://medicalxpress.com/news/2025-09-key-driver-pancreatic-cancer.html