Molecular mechanisms in the development of pancreatic cancer
Gastroenterology
Final Report Abstract
Our results indicate that mice with the acinar cell promotor Ptf1α develop PanIN lesions and pancreatic cancer. Our supports the hypothesis of acinar cells as the original cells for PanIN lesions and PDAC. Furthermore, our study shows for the first time that the Hnf1β mice do not develop any pancreatic lesions so that ductal cells are not the original cell type of pancreatic cancer. Our study and collaboration revealed a novel collaborative cell interaction in cancer, in which senescent cells drive the growth of premalignant pancreatic lesions. Pharmacologic elimination of senescent cells through senolytic therapy may be beneficial in prevention of disease progression. Future work will focus on further studies of senescence during pancreatic cancer development, in particular epigenetic aspects such as DNA methylation and chromatin changes, towards development of better senolytic drugs as well as the developmet of circulating cell-free DNA biomarkers that can identify cell death in the senescent population. These studies will be performed in collaboration between the Israeli and Palestinian partner.
