“Tackling Pancreatic cancer growth promoting cancer stem cell differentiation”
Pancreatic cancer is a lethal disease, with one of the worst prognoses among solid tumors. Recent studies support that pancreatic metastasis is invariably associated with homeostasis alteration of endogenous pancreatic stem cells defined pancreatic Cancer Stem Cells (pCSCs). The pCSCs are characterized by the ability to initiate and fuel tumor growth. Current oncological therapies are mainly able to inhibit high proliferative cancer cells, while showing no effects on quiescent pCSCs that are responsible for cancer relapse, and hence, for tumor aggressiveness. In the light of this, inducing pCSCs differentiation could provide an alternative way to inhibit cancer growth.
Our project is based on the hypothesis that a valuable approach to induce pCSCs differentiation is to treat them with molecules able to enhance signaling pathways associated to pancreatic Stem Cells differentiation during normal pancreas organogenesis. In particular, we aim to identify chemical compounds capable to hamper growth and metastatic phenotype of pancreatic tumors by inducing pCSCs differentiation. First year, will be focused on pCSs isolation from pancreatic mouse model, and genetically modification using innovative CRISPR/Cas9 methodology. Furthermore, during the second year we expect to unveil promising chemotherapeutic assay aimed to prime pCSCs in vitro differentiation through liquid handling robotics (automated systems) preparation for high throughput screening, and High-content screening (HCS) technologies. For most encouraging pro-differentiation drugs, on the third year we plan to assess effects on tumor development in vivo, by injecting pCSCs treated cells into nude mice and analyze their fate.
Completion of the proposed studies will provide a directed strategy for novel therapeutics to specifically target the cancer cellular population responsible for the recurrence of pancreatic tumors.
This job comes from a partnership with Science Magazine and