Tumor dormancy due to failure of angiogenesis: role of the microenvironment

Tumor progression is dependent on a number of sequential steps, including initial recruitment of blood vessels (i.e., angiogenic switch). Failure of a microscopic tumor to complete one or more of these early steps may lead to delayed clinical manifestation of the cancer. In this review we summarize some of the clinical and experimental evidence suggesting that microscopic human cancers can remain in an asymptomatic, non-detectable, and occult state for the life of a person or animal. We present three clinical cases where tumors present shortly after an accidental trauma in otherwise healthy individuals. We also review current experimental human tumor dormancy models with special emphasis on the angiogenic switch which closely recapitulates clinically observed delay in tumor recurrence.