Unveiling cancer dormancy: Intrinsic mechanisms and extrinsic forces

Tumor cells disseminate in various distant organs at early stages of cancer progression. These disseminated tumor cells (DTCs) can stay dormant/quiescent without causing patient symptoms for years or decades. These dormant tumor cells survive despite curative treatments by entering growth arrest, escaping immune surveillance, and/or developing drug resistance. However, these dormant cells can reactivate to proliferate, causing metastatic progression and/or relapse, posing a threat to patients' survival. It's unclear how cancer cells maintain dormancy and what triggers their reactivation. What are better approaches to prevent metastatic progression and relapse through harnessing cancer dormancy? To answer these remaining questions, we reviewed the studies of tumor dormancy and reactivation in various types of cancer using different model systems, including the brief history of dormancy studies, the intrinsic characteristics of dormant cells, and the external cues at the cellular and molecular levels. Furthermore, we discussed future directions in the field and the strategies for manipulating dormancy to prevent metastatic progression and recurrence.