Prostate carcinogenesis: inflammatory storms

• Published in: Nature reviews. Cancer Vol. 20; no. 8; pp. 455 - 469
• Main Authors: de Bono, Johann S., Guo, Christina, Gurel, Bora, De Marzo, Angelo M., Sfanos, Karen S., Mani, Ram S., Gil, Jesús, Drake, Charles G., Alimonti, Andrea
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2020; Nature Publishing Group
• Subjects: 631/250/256; 631/337/1427/2566; 631/67/327; 631/67/589/466; Androgen receptors; Androgens; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinogenesis; Carcinogenesis - genetics; Carcinogenesis - immunology; Cell activation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - immunology; Chronic Disease; Deoxyribonucleic acid; Development and progression; Diet - adverse effects; Dietary Fats - adverse effects; Dietary Fats - immunology; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA Damage - genetics; DNA Damage - immunology; DNA repair; DNA Repair - genetics; DNA Repair - immunology; Epithelial cells; Free radicals; Health aspects; Humans; Inflammation; Inflammation - etiology; Inflammation - genetics; Inflammation - immunology; Male; Microbiomes; Microbiota - immunology; Morbidity; Obesity - complications; Obesity - immunology; Paracrine Communication - immunology; Phenotypes; Prostate - immunology; Prostate cancer; Prostatic Neoplasms - etiology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - immunology; Receptor mechanisms; Receptors, Androgen - genetics; Receptors, Androgen - immunology; Review Article; Risk factors; Senescence; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumor suppressor genes; Tumorigenesis; Tumors
• ISSN: 1474-175X; 1474-1768; 1474-1768
• DOI: 10.1038/s41568-020-0267-9

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. This Review discusses intra-prostatic inflammatory processes and how they are induced and perpetuated, thereby driving prostate cancer development and progression. By discussing external inflammatory cues in connection to cancer cell-intrinsic factors in prostate tumorigenesis, the authors provide insight into potential preventative and therapeutic strategies.