The senescence pathway in prostatic carcinogenesis.

Prostate cancer is a disease of the old and with increasing life expectancy, its incidence will continue to increase in the future. Control of prostate cancer has involved androgen ablation as a routine form of therapy. However, after an initial response, therapy-resistant clones can appear and result in cancer progression and metastasis with high mortality. The precise mechanisms for the development of androgen resistance are yet uncertain. It appears to be multi-factorial and relates not only to newly acquired genomic capabilities of the cancer cells but also to their interaction with their microenvironment. Overcoming cellular senescence is essential for oncogenesis. Although it seems to be a protective response for normal cells to avoid malignant transformation, senescence can on the other hand promote tumour progression. Interaction of senescent cancer cells with their microenvironment may be the key link to survival or regression of neoplastic cells. Hence, there is speculation that senescence may be a useful new target for therapy in the future. We review the role of senescence in prostate cancer and the effect of tumour microenvironment on androgen resistance.