Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications

Since the discovery of cancer cells with stem-like characteristics in hematopoietic malignancies and, more recently, in solid tumors, enormous attention has been paid to the stem-cell nature of pancreatic cancer. Among the most important properties of cancer stem cells their high capacity for tumorigenicity as well as their ability to metastasize is under special research interest today.

Here, we give a brief overview of main components used to confirm the stem-cell-like behavior of putative cancer stem cells and discuss markers and methods for identifying them in pancreatic cancer. Finally, the review provides some new suggestions as to how specifically target these cells and improve current therapy regimens.

The cancer stem-cell hypothesis is a fundamentally different model of carcinogenesis composed of two separate but dependent on each other characteristics of stem cells--aberrant activation of their tightly regulated processes of self-renewal and differentiation and their resistance towards chemo- and radiotherapy. The cancer stem cells may further be identified based on their expression of cell surface markers or their functional characteristics. The concept of molecular targeting of such highly tumorigenic cancer cells aimed to sensitize tumors toward conventional therapies and effectively abrogate tumor growth and metastasis.

The presence of cancer stem cells in pancreatic tumors has prognostic relevance and influences therapeutic response. Evidence suggests that metastatic potential may be conferred to these highly tumorigenic cells as well. A better understanding of the biological behavior of these cells may further improve therapeutic approaches and outcomes in patients with this devastating disease.