BACKGROUND: Solid tumours are the most common cancers and represent a major therapeutic challenge. The cancer stem cell (CSC) 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. OBJECTIVE: Here we review the most recent advances in the CSC 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. METHODS: This review focuses on the role of CSC in the promotion and metastasis of solid tumours and summarizes recent findings regarding the targeting of signalling pathways that are of particular importance for the maintenance and the elimination of CSC as the proposed root of the tumour. RESULTS/CONCLUSIONS: There is increasing evidence that solid tumours, including pancreatic cancer, are hierarchically organized and sustained by a distinct subpopulation of CSC. Direct evidence for the CSC hypothesis has emerged from mouse models only recently. While the clinical relevance of CSC remains a fundamental issue, current findings suggest that specific targeting of these cells is possible and therapeutically relevant.
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