Prostate Carcinogenesis: Inflammatory Storms

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2020 Jun 18

PMID 32546840

Citations 93

Authors

Johann S de Bono

Christina Guo

Bora Gurel

Angelo M De Marzo

Karen S Sfanos

Ram S Mani

Jesus Gil

Charles G Drake

Andrea Alimonti

Affiliations

Soon will be listed here.

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.

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