Clinical opportunities and challenges in targeting tumour dormancy

The reactivation of cancer cells following a seemingly successful treatment of the primary tumour with initial therapies (such as tumour excision or systemic therapy) is a well-known phenomenon. This metastatic rebirth is preceded by an interlude, termed dormancy, when cancer sleeps undetected for periods that can last years or even decades. Discoveries over the past 10 years have revealed the therapeutic potential of prolonging dormancy for maintaining a clinically asymptomatic state, or the permanent clearance of dormant residual disseminated cancer cells to affect a 'cure'. Here, we provide an overview of the mechanisms of dormancy and use genitourinary cancers as models to demonstrate how dormancy principles could be exploited clinically. Data from these models have yielded promising therapeutic strategies to address dormancy as well as diagnostics that could enable clinicians to monitor the dormant state of cancer in patients. This Review also aims to convey that dormancy, as a whole, likely results from coalescing contributions made by each of the three types of dormancy discussed (cellular, angiogenic and immunological). In our opinion, dormancy-directed therapies will prove most effective when the effect of these cumulative contributions are understood and targeted.