Prostate carcinogenesis: inflammatory storms

JS de Bono, C Guo, B Gurel, AM De Marzo… - Nature Reviews …, 2020 - nature.com
Nature Reviews Cancer, 2020nature.com
Prostate cancer is a major cause of cancer morbidity and mortality. Intra-prostatic
inflammation is a risk factor for prostate carcinogenesis, with diet, chemical injury and an
altered microbiome being causally implicated. Intra-prostatic inflammatory cell recruitment
and expansion can ultimately promote DNA double-strand breaks and androgen receptor
activation in prostate epithelial cells. The activation of the senescence-associated secretory
phenotype fuels further 'inflammatory storms', with free radicals leading to further DNA …
Abstract
Prostate cancer is a major cause of cancer morbidity and mortality. Intra-prostatic inflammation is a risk factor for prostate carcinogenesis, with diet, chemical injury and an altered microbiome being causally implicated. Intra-prostatic inflammatory cell recruitment and expansion can ultimately promote DNA double-strand breaks and androgen receptor activation in prostate epithelial cells. The activation of the senescence-associated secretory phenotype fuels further ‘inflammatory storms’, with free radicals leading to further DNA damage. This drives the overexpression of DNA repair and tumour suppressor genes, rendering these genes susceptible to mutagenic insults, with carcinogenesis accelerated by germline DNA repair gene defects. We provide updates on recent advances in elucidating prostate carcinogenesis and explore novel therapeutic and prevention strategies harnessing these discoveries.
nature.com