Label retaining cells in cancer – The dormant root of evil?

• In some tissues, a sub-population of normal adult stem cells is dormant.
• Dormant, label retaining tumor cells might be responsible for relapse.
• Tumor relapse may be initiated from label-retaining tumor cells.
• Tumor cell dormancy can be regulated by internal or microenvironmental cues.
• Dormancy may be a mechanism through which tumor cells evade therapeutic intervention.

The phenomenon of cellular dormancy has been observed in normal adult stem cells in many different tissues such as the skin, the intestine and the hematopoietic system. These dormant cells have been proposed to be important for life-long self-renewal and for the generation of the different cellular lineages. As tumor cells can share properties with normal stem cells, dormant cells might also exist within a tumor. The term tumor dormancy has evolved from the clinical observation in cancer patients that relapse can occur years to decades after apparently successful treatment, suggesting that some cancer cells might resist chemotherapy and persist in a dormant state. Several studies investigating the role of cellular dormancy in normal stem cells and in cancer hint towards a complex network involving different pools of cells. These cells might interact with each other or even dynamically switch their phenotypes dependent upon so far unknown endogenous and microenvironmental stimuli. In this review, we will discuss the recent findings related to cellular dormancy in normal adult stem cells and in cancer. Furthermore, the clinical relevance of dormancy and its dynamic regulation in tumor cells will be highlighted.