Pancreatic adenocarcinoma (PDAC) is one of the most aggressive and devastating human malignancies with a mortality projected to surpass that of breast and colorectal cancer by 2030 in the United States. This tumour is highly metastatic and is characterised by resistance to chemotherapy and radiation. In a mouse model of PDAC, it has been demonstrated that cellular dissemination leading to metastasis occurs prior to the formation of an identifiable primary tumour. This behaviour is associated with the establishment of circulating pancreatic cells that express typical markers of cancer stem cells (CSCs). Evidence for the existence of CSCs in primary human PDAC has also been provided and it has been shown that these cells are more resistant to therapeutic agents compared to more differentiated tumour cells. The DNA alterations and the related gene expression at the basis of the induction of the CSC properties are still largely unknown. Thus, the identification of CSC specific molecular features is crucial for the development of efficient PDAC therapies that should be specifically directed against CSCs. In this respect, nanomedicine has great potential in the development of CSC-targeting drugs, controlled drug delivery and release, and the design of novel gene-specific drugs.
Through the synergistic collaboration with the CNRS Unit of Chatenay-Malabry in France, directed by Prof. Elias Fattal, the present proposal aims at characterizing the molecular profiles of CSCs from several PDAC cell lines to identify targets for therapies directed against PDAC CSCs and to develop drug containing nanoparticles directed against these cells. Since one of the major concern about PDAC is its high resistance to traditional therapies most likely due to the presence of CSCs, the ultimate goal of this project is the development of nanoparticle based therapy capable of improving the prognosis of PDAC patients.
