The Events Leading to Pancreatic Cancer Onset

A pancreatic cancer diagnosis is especially devastating for patients since the prognosis for recovery is typically poor; this is because the cancer is most often not detected until late stages. Researchers have now uncovered new data concerning the tumor-initiating events that leads to pancreatic cancer in mice. Published in the journal Cancer Cell, their work may aid in the search for earlier detection methods and treatments.

Co-principal investigator of the study, Mike Sander, MD, claims, “Previously, it was believed that this cancer arises from the epithelial cells in pancreatic ducts. But in this study, we show that ducts have almost no response to oncogenic mutations – mutations that give rise to cancerous tumors.”

The study uncovered evidence that another pancreatic cell type, known as the acinar cell, changes into a duct-like cell that initiates tumor growth. The researchers also demonstrated that inflammation of the pancreas, which is a significant risk factor for pancreatic cancer, increases the rate that acinar cells transform into duct-like tumor precursors.

Kras is a gene that may lead to cancer development when it is mutated. The gene is responsible for creating the Kras protein, which is involved in cell signaling pathways, cell growth and cell death. Compounds that inhibit the function of the mutated Kras gene or its protein may block the proliferation of cancer.

Following specific cell populations in the presence and absence of tissue injury in mice, the research team showed that a mutated Kras gene can readily induce premalignant lesions from adult acinar cells, but not from ductal cells. Adult acinar cells are far more abundant than ductal cells in the adult pancreas and can generate premalignant lesions at a rate 100 times greater than ductal cells.

Researchers also discovered that when these lesions are formed by acinar cells, a transcription factor known as Sox9 becomes active. Overexpression of this gene enhances the abnormal changes necessary for cancer growth to begin, unchecked. The researchers suggest that Sox9 could be a potential treatment target to prevent early tumor-initiating events in the pancreas.