Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance. A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. In recent years, the cancer stem cell (CSC) theory has changed the classical view of tumor growth and therefore the therapeutic perspective. Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. On the other hand, the identification of CSCs in vivo and in vitro relies on specific surface markers that should allow the sorting cancer cells into phenotypically distinct subpopulations. In the present review, recent papers published on CSCs in solid tumors (breast, prostate, brain and melanoma) are discussed, highlighting critical points such as the choice of markers to sort CSCs and mouse models to demonstrate that CSCs are able to replicate the original tumor. A discussion of the possible role of aldehyde dehydrogenase and CXCR6 biomarkers as signaling molecules in CSCs and normal stem cells is also discussed. The author believes that efforts have to be made to investigate the functional and biological properties of putative CSCs in cancer. Developing diagnostic/prognostic tools to follow cancer development is also a challenge. In this connection it would be useful to develop a multidisciplinary approach combining mathematics, physics and biology which merges experimental approaches and theory. Biological models alone are probably unable to resolve the problem completely.
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