Dormant disseminated tumor cells and cancer stem/progenitor-like cells: Similarities and opportunities

Abstract

Distant recurrences occurring years after removal of the primary tumor arise from disseminated tumor cells (DTCs) that lie dormant (quiescent/asymptomatic) until they emerge to overt metastases. These quiescent DTCs are resistant to conventional treatments. Hence, to date there is no available treatment which targets dormant DTCs before they form overt metastases. Therefore, understanding the biology of dormant DTCs and the mechanisms of their reactivation is vital in our pursuit to develop therapies to prevent cancer from ever recurring. This review will address the striking similarities between the biology of DTCs and the biology of cancer stem cells (CSCs) or CSC-like cells including cancer progenitor-like cells. These similarities are related to intrinsic mechanisms of survival and quiescence, and their cross-talk with mediators, produced in their surrounding niches that may support either dormancy or outgrowth. Unraveling these similarities may provide us with exciting opportunities to either mitigate the survival of residing dormant DTCs/CSCs or maintain them in a dormant state. Whether the stemness properties of CSCs/cancer progenitor-like cells already comprising the recurring tumor can be exploited in order to differentiate them, and thus promote their dormancy, will be explored as well. Overall, these emerging concepts may provide us with new opportunities to prevent lethal recurrences.

Keywords: Cancer stem cells; Differentiation therapy; Disseminated tumor cells; Tumor dormancy; Tumor microenvironment.