At the root of pancreatic cancer’s aggressiveness is a particular transformation that pancreatic cells undergo, making them capable, even in the early stages of the disease, of forming metastases and resisting therapy. This is what researchers from the MD Anderson Cancer Center in Houston, led by Giannicola Genovese, discovered in a study published in Nature.

"Pancreatic cancer is highly aggressive, metastasizes quickly, and is very difficult to treat," explains the lead author of the research, Luigi Perelli. The study also involved researchers from IRCCS San Raffaele in Milan, the Catholic University of the Sacred Heart, and the Policlinico Foundation in Rome.

"For over a decade, research has been studying a particular type of cell observed in various cancers during advanced stages of the disease: these are called ‘mesenchymal-like tumor cells,’ and they result from a transformation of epithelial cells—the cells that line the surface of organs—that become more mobile and invasive." This transformation is known as the 'epithelial-to-mesenchymal transition,' and until now, it was unclear whether it provided any advantage to the tumor. "In our new study, we discovered that not only is it important, but in the case of pancreatic cancer, it plays a key role in its aggressiveness," adds Perelli.

The 'epithelial-to-mesenchymal transition,' the study continues, has several consequences: on one hand, it generates tumor cells with greater ability to spread, and on the other, it creates instability in the tumor cells' genome, leading to greater heterogeneity in the cells that make up the tumor. The result is an enhanced ability of the tumor to adapt to unfavorable conditions and therapies. As if that weren’t enough, "this transformation, which occurs in advanced stages of other cancers, happens almost immediately in pancreatic cancer."

"This explains the extreme difficulty in identifying an effective treatment for this cancer," adds Perelli. "Our work is critical for clarifying the evolutionary patterns underlying the aggressive clinical behavior of pancreatic cancer," comments Giannicola Genovese. "These results add another layer to our understanding of tumor heterogeneity and the complexity of the cancer microenvironment, providing new crucial insights for treating this devastating disease."

The research could pave the way for new treatments capable of selectively targeting cells with mesenchymal characteristics, thus depriving the tumor of its main driver.