Mechanisms of disseminated cancer cell dormancy: an awakening field

Disseminated tumour cells that survive treatment may become dormant and their 'awakening' may be the source of metastases. This Review discusses the mechanisms and factors that regulate tumour dormancy, including the extracellular and stromal microenvironments, autophagy and epigenetics. The authors also discuss how this information could be used therapeutically for metastatic disease. Metastases arise from residual disseminated tumour cells (DTCs). This can happen years after primary tumour treatment because residual tumour cells can enter dormancy and evade therapies. As the biology of minimal residual disease seems to diverge from that of proliferative lesions, understanding the underpinnings of this new cancer biology is key to prevent metastasis. Analysis of approximately 7 years of literature reveals a growing focus on tumour and normal stem cell quiescence, extracellular and stromal microenvironments, autophagy and epigenetics as mechanisms that dictate tumour cell dormancy. In this Review, we attempt to integrate this information and highlight both the weaknesses and the strengths in the field to provide a framework to understand and target this crucial step in cancer progression.