Tumor Dormancy: Biologic and Therapeutic Implications

Metastatic cancer can arise years after treatment of the primary tumor because residual tumor cells can enter dormancy and evade elimination by anti-neoplastic therapies. The mechanisms underlying this phenomenon have been investigated and a number of hypotheses have been proposed. Tumor mass dormancy involves a balance between apoptotic and proliferative cells, keeping a micrometastatic lesion constant in size. This induces a need for blood supply which involves angiogenic dormancy. Cellular dormancy is also considered a mechanism of dormancy, where dormancy is induced due to cells entering a quiescent, reversible, growth-arrested state. In addition to all of these mechanisms, important changes in the tumor microenvironment, including the extracellular matrix, the oxygenation levels of the environment, and endoplasmic reticulum stress, are involved in inducing and maintaining tumor dormancy. Since dormant tumors are commonly known to be resistant to chemotherapy, gaining more knowledge of the mechanism of dormant tumor cells is of importance, as it can lead to the development of future treatment strategies.