Pancreatic cancer is associated with poor prognosis in patients due to therapy resistance and presence of advanced or metastatic disease at point of diagnosis. Pancreatic tumors are comprised of numerous states driven by gene expression and genetic alterations that confound our understanding of therapy response. Despite several decades of therapeutic advancement in the clinic, long-term survival rates following pancreatic cancer diagnosis remain low. Therefore, there is a need for a deeper understanding of how these states can alter therapeutic responses.
Senescence is a cellular stress response driven by damage that results in halting of cell division and inflammation in tissues. This carefully orchestrated response is mediated through regulation of a complex network of genes. In cancer, senescence has been observed as a response to conventional chemotherapeutic drugs and can alter the surrounding tumor microenvironment (TME). These effects are driven through secretion of a diverse array of inflammatory signaling molecules. The composition of these inflammatory molecules and their implication on the TME are poorly understood. Dr. McHugh plans to investigate this question further using mouse models of senescence induction in pancreatic cancer combined with advanced imaging and genetic perturbation techniques. He will investigate (I) what shapes inflammatory response during senescence and (II) what effects different inflammatory responses have in pancreatic cancer. This project will form the basis for further development of combinatorial therapies to better engage the immune system in pancreatic cancer.
Projects and Grants
Deconvoluting the interplay between senescence inflammatory heterogeneity and PDAC
Memorial Sloan Kettering Cancer Center | Pancreatic Cancer | 2024 | Scott W. Lowe, PhD
