Integrative mechanobiology and genomics profiling of resistance patterns to foster novel therapeutics in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that is notoriously chemoresistant. Despite extensive genetic mapping, the identification of specific subtypes, and the realization that the tumor microenvironment, including desmoplasia, contributes to chemoresistance, the clinical perspective for PDAC patients remains grim. Tumors have been described to mechanically alter their microenvironment, for instance through extracellular-matrix (ECM) stiffening, which in turn drives survival and growth of tumor cells. Interestingly, PDAC is extremely rich in ECM suggesting that such a positive feedback loop is highly relevant in this context. Indeed, recent reports implicate biomechanical aspects of PDAC-stroma interactions in PDAC progression. We were able to further substantiate and extend those observations. Our new findings suggest that the force-transducing cell adhesion signaling machinery (integrins, FAK/Src) contributes to the chemoresistant phenotype of PDAC.
In this project, we will investigate how PDAC cells stiffen their environment and how this in turn affects growth and chemoresistance of cells, unravel the underlying molecular machinery that leads to mechano-chemical feedback, and identify new targets to interfere with this process for the development of new therapeutic strategies.
Cecilia and Alessandro – welcome to the team!