Patterns of indolence in prostate cancer (Review).

Although prostate cancer is a major cause of cancer-related mortality worldwide, most patients will have a relatively indolent clinical course. Contrary to most other types of cancer, even the diagnosis of locally advanced or metastatic disease is not always lethal. The present review aimed to summarize what is known regarding the underlying mechanisms related to the indolent course of subsets of prostate cancer, at various stages. The data suggested that no specific gene alteration by itself was responsible for carcinogenesis or disease aggressiveness. However, pathway analysis identified genetic aberrations in multiple critical pathways that tend to accumulate over the course of the disease. The progression from indolence into aggressive disease is associated with a complex interplay in which genetic and epigenetic factors are involved. The effect of the immune tumor microenvironment is also very important. Emerging evidence has suggested that the upregulation of pathways related to cellular aging and senescence can identify patients with indolent disease. In addition, a number of tumors enter a long-lasting quiescent state. Further research will determine whether halting tumor evolution is a feasible option, and whether the life of patients can be markedly prolonged by inducing tumor senescence or long-term dormancy.