Using approaches first applied in human leukemias, recent progress has been made in the identification of putative cancer stem cells in several different carcinomas and other solid cancers. Additional studies have suggested that cancer stem cells may be derived not only from transformation of quiescent, long-term stem cells but also from short-lived progenitors that then obtain the ability to undergo self-renewal. Therefore, the heterogeneity observed in many types of human cancers may reflect both the activation of specific oncogenes and/or loss of specific tumor suppressor genes and the different stem and/or progenitor cell populations in which these genetic or epigenetic events occur. Similarities have been observed in the pathways regulating stem cell homing and metastasis, and increasing evidence also suggests that treatment failure and the recurrence of human cancer may reflect the intrinsic quiescence and drug resistance of cancer stem cells.
Conclusions
Despite the explosion of new information and the exponential number of publications in the past few years in the ‘cancer stem cell’ field, much remains to be learned. There is a need for better cell-lineage markers for the multiple cell types present in most tissues, and for better reagents to facilitate the isolation of these cells in order to enable the identification of the cells of origin for the different subtypes of cancers. Little information is currently available about the nature of the stem cell niche and the pathways regulating quiescence and self-renewal in both normal tissue stem cells and cancer stem cells. In summary, although recent progress has been encouraging, the differences in signaling pathways in normal and cancer stem cells need to be elucidated to provide new therapeutic targets with the eventual goal of eliminating residual disease and recurrence.
