Study offers insights into evolutionary process driving pancreatic cancer aggressiveness
MD Anderson News Release March 05, 2025
Pancreatic cancer is hard to treat because of its heterogeneity, a characteristic frequently sustained by the ability of cells to change states. One example is epithelial-to-mesenchymal transition (EMT), in which epithelial cells become more mobile. While EMT plays a critical role in many cellular processes, cancer cells have leveraged EMT to promote treatment resistance and metastasis. To better understand its functional role in cancer progression and evolution, Luigi Perelli, M.D., Ph.D., Giannicola Genovese, M.D., Ph.D., and collaborators established genetically engineered lab models that allowed them to examine tumors derived directly from cell lineages undergoing EMT. They discovered that EMT is a necessary step for epithelial tumors to become malignant. Tumors with mesenchymal features also have increased chromatin accessibility and genomic instability – particularly through the breaking and rearrangement of chromosomal pieces – leading to increased heterogeneity within the tumor, which is favored by EMT across lineages. These findings support the concept of restricted patterns of evolution within specific cell states, providing valuable insights into how tumors acquire heterogeneity and strategies to target pancreatic cell progression. Learn more in Nature.
This work is instrumental in clarifying the evolutionary patterns and characteristics of aggressive pancreatic cancer, providing evidence of cell-state specific evolutionary pathways in epithelial cancers. We show that phenotype can shape the genomic landscape of cancer, adding to our understanding of tumor heterogeneity and the complexity of the cancer ecosystem.