Pancreatic cancer stem cells – update and future perspectives

Abstract 

Solid tumours are the most common cancers and represent a major therapeutic challenge. The cancer stem cell hypothesis is an attractive model to explain the functional heterogeneity commonly observed in solid tumours. It proposes a hierarchical organization of tumours, in which a subpopulation of stem cell-like cells sustains tumour growth, metastasis, and resistance to therapy. We will present the most recent advances in the cancer stem cell field, with particular emphasis on pancreatic cancer as one of the deadliest human tumours, and highlight open questions and caveats to be addressed in future studies. There is increasing evidence that solid tumours including pancreatic cancer are hierarchically organized and sustained by a distinct subpopulation of cancer stem cells. However, direct evidence for the validity of the cancer stem cell hypothesis in human pancreatic cancer remains controversial due to the limitations of xenograft models but supportive data are now emerging from mouse models using related or different sets of markers for the identification of murine cancer stem cells. Therefore, while the clinical relevance of cancer stem cells remains a fundamental issue for this rapidly emerging field, current findings clearly suggest that specific elimination of these cells is possible and therapeutically relevant. Targeting of signalling pathways that are of particular importance for the maintenance and the elimination of cancer stem cell as the proposed root of the tumour may lead to the development of novel treatment regimens for pancreatic cancer. Here we will review the current literature on pancreatic cancer stem cells and the future perspective of this rapidly emerging field.

Keywords: Pancreatic cancer, Stem cells, Cancer stem cells, Tumour-initiating cell, metastasis, mTOR, Hedgehog, Gemcitabine, Targeted therapy