Although the hypothesis that tumours are maintained by cancer stem cells is being intensively researched, it remains controversial. Three studies now use genetic lineage tracing to track cancer stem cells in vivo, providing support for this model of sustaining tumour growth.

Using elegant genetic lineage tracing approaches, Clevers and co-workers (Science 337, 730–735; 2012) identified cells with stem cell characteristics in mouse intestinal adenomas. Distinguished by Lgr5, a marker of normal intestinal crypt stem cells, these cells displayed gene expression signatures, clonogenic properties and localization architecture similar to that of normal crypt stem cells. Simons, Blanpain and colleagues (Nature http://doi.org/h56; 2012) also employed lineage tracing to analyse the fate of genetically labelled tumour cells in mouse models of benign papilloma and squamous skin carcinoma. The authors' characterization of tumour growth modes demonstrated the existence of tumour cells with stem-cell-like properties. In a parallel study, Parada and colleagues (Nature http://doi.org/h57; 2012) showed in a glioma mouse model that tumour cells genetically labelled with Nestin–GFP, a marker of adult neural stem cells, have properties consistent with those of cancer stem cells. These cells were able to reinitiate tumour growth following chemotherapeutic inhibition of proliferation, whereas specific elimination of the cancer stem cells significantly impaired tumour growth.

These exciting findings will fuel studies to trace cancer stem cells in other tumour types, and to develop therapies to specifically target and eliminate them.