Pancreatic cancer is notoriously difficult to treat, resulting in a five-year survival rate of roughly 12%. Approximately half of patients develop metastases shortly after diagnosis, but the biological mechanisms driving spread to specific organs are not fully understood.
To provide insights, Linghua Wang, M.D., Ph.D., Anirban Maitra, M.B.B.S., and colleagues generated a comprehensive spatial atlas using 55 samples of primary tumors and metastases collected from 13 patients with advanced pancreatic cancer undergoing rapid autopsy. The researchers focused on mapping clonal evolution, cancer cell states and tumor microenvironment changes, which they validated using patient-derived models. This high-resolution approach highlighted noticeable lineage shifts in cancer cells transitioning from the primary tumor site to organ-specific metastases. It also provided a visualization of the two distinct epithelial states that are characterized by unique gene expression profiles and prognostic implications. These findings emphasize the importance of considering transcriptomic diversity and changes in the tumor microenvironment when identifying potential biomarkers and therapeutic targets for treatment-resistant pancreatic cancer.