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Abstract

Dormancy has been defined as "one of two prerequisites for life" and plays a fundamental role in all stages of tumor evolution. Described as a reversible quiescent cellular stage, tumor dormancy allows adaptation and survival of tumor cells under hostile conditions, for example, oxidative or metabolic stress, inflammatory processes or exposure to anticancer therapies. Thus, dormant tumor cells are fundamental for the fitness of the entire tumor cell population assuring and promoting tumor evolution so that dormancy has been postulated as a novel hallmark of cancer. Besides the tumoral microenvironment, epigenetic, and metabolic alterations seem to be critical determinants for the entry in and exit from dormancy. However, the underlying mechanisms are still poorly understood. In fact, dormant life-history phases or stages are widespread among living organisms representing a highly effective strategy to survive unfavorable environmental conditions and thus ensuring persistence during evolution. Integrating an evolutionary perspective in the investigation of tumor dormancy will help us to understand the plasticity of the proliferative phenotype of tumor cells and how this promotes tumor evolution. Incorporating evolutionary methods into cancer research and addressing new evolutionary questions may help to explain the phenomenon of dormancy in tumor evolution leading to improved cancer therapies. © 2017 Elsevier Inc. All rights reserved.