The proto-oncogene nonreceptor
tyrosine-protein kinase SRC is a member of the SRC family of
tyrosine kinases (SFKs), and its activation and overexpression have been shown to play a protumorigenic role in multiple solid
cancers, including pancreatic ductal
adenocarcinoma (PDAC). PDAC is currently the seventh-leading cause of
cancer-related death worldwide, and, by 2030, it is predicted to become the second-leading cause of
cancer-related death in the United States. PDAC is characterized by its high lethality (5-year survival of rate of <10%), invasiveness, and chemoresistance, all of which have been shown to be due to the presence of
pancreatic cancer stem cells (PaCSCs) within the
tumor. Due to the demonstrated overexpression of SRC in PDAC, we set out to determine if
SRC kinases are important for PaCSC biology using pharmacological inhibitors of
SRC kinases (
dasatinib or PP2). Treatment of primary PDAC cultures established from patient-derived xenografts with
dasatinib or PP2 reduced the clonogenic, self-renewal, and
tumor-initiating capacity of PaCSCs, which we attribute to the downregulation of key signaling factors such as p-FAK, p-ERK1-2, and p-AKT. Therefore, this study not only validates that
SRC kinases are relevant and biologically important for PaCSCs but also suggests that inhibitors of
SRC kinases may represent a possible future treatment option for PDAC patients, although further studies are still needed.