Mechanisms of Metastatic Tumor Dormancy

Abstract

Tumor metastasis can occur years after an apparent cure due to a phenomenon known as metastatic tumor dormancy; in which tumor masses or individual tumor cells are growth restricted for extended periods of time. This period of dormancy is induced and maintained by several mechanisms, including: (1) Tumor microenvironment factors such as cytokine expression, immunosurveillance and angiogenesis; (2) Metastasis suppressor gene activity; and (3) Cancer therapeutics. Disseminated tumor cells (DTC) are the key cells that result in dormant tumors. However, many challenges exist towards isolating DTCs for mechanistic studies. The main DTC that may represent the dormant cell is the cancer stem cells (CSC) as they have a slow proliferation rate. In addition to limited knowledge regarding induction of tumor dormancy, there are large gaps in knowledge regarding how tumors escape from dormancy. Emerging research into cancer stem cells, immunotherapy, and metastasis suppressor genes, may lead to new approaches for targeted anti-metastatic therapy to prevent dormancy escape. Overall, an enhanced understanding of tumor dormancy is critical for better targeting and treatment of patients to prevent cancer recurrence.

Keywords: dormancy; tumor cell dormancy; tumor mass dormancy.

Figure 1

Schematic of metastatic tumor dormancy. Some tumor cells will leave the primary tumor without the ability to proliferate in the new microenvironment and remain as solitary cells (tumor cell dormancy), due to microenvironmental-induced stress, microenvironment incompatibility or even a gene expression profile that is prone to dormancy. Some tumor cells can leave the primary site with the ability to proliferate in the new site, but cannot grow beyond a few mm (tumor mass dormancy) due to immunosurveillance or angiogenic failure.