The Relationship Between Dormant Cancer Cells and Their Microenvironment

The majority of cancer deaths are due to metastases that can occur years or decades after primary tumor diagnosis and treatment. Disseminated tumor cells (DTCs) surviving in a dormant state in target organs appear to explain the timing of this phenomenon. Knowledge on this process is important as it might provide a window of opportunity to prevent recurrences by eradicating dormant DTCs and/or by maintaining DTCs in a dormant state. Importantly, this research might offer markers of dormancy for early monitoring of metastatic relapse. However, our understanding of the mechanisms underlying the regulation of entry into and exit from dormancy is still limited and crippling any therapeutic opportunity. While cancer cell-intrinsic signaling pathways have been linked to dormancy regulation, it is likely that these pathways and the switch controlling reactivation from dormancy are regulated by microenvironmental cues. Here we review and discuss recent findings on how the microenvironment regulates cancer dormancy and raise new questions that may help advance the field.