Prostate carcinogenesis: inflammatory storms

Abstract

Prostate cancer (PCa) 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. Inflammation can expand intra-prostatic myeloid cells that promote immunosuppression, DNA double-strand breaks, and activate androgen receptor (AR) target genes. AR signalling and free radicals mediate further DNA damage, thereby driving the chronic activation of DNA repair genes (DRG) and tumour suppressor genes, rendering them more susceptible to endogenous and exogenous mutagens. These processes are accelerated in the context of germline DRG defects. We provide an update on recent advances in our understanding of the mechanisms through which inflammation and immune-dysregulation facilitate prostate carcinogenesis. We explore novel therapeutic and prevention strategies harnessing these discoveries.

Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19

“…The host immune response to SARS-CoV-2 potentiates a hyper-inflammatory cytokine storm involving the upregulation of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1 β), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 1-α (MIP1α), which is associated with COVID-19 severity and mortality(Mehta et al, 2020; Moore and June, 2020; Vabret et al, 2020; Zhang et al, 2020). Tumor cell-intrinsic and microenvironment associated immune cell response to inflammation promote the development and progression of several types of solid cancer, including prostate cancer (de Bono et al, 2020). Therefore, it is reasonable to hypothesize that the inflammatory signaling accompanying severe COVID-19 disease could cause cancer progression.…”

<p>Circ_0062020 Knockdown Strengthens the Radiosensitivity of Prostate Cancer Cells</p>

“…1 The putative major risk factors to PCa were listed as chronic inflammation, genetic factors and the occurrence of metastatic castration-resistant prostate cancer. 2 Despite the extraordinary progress in PCa treatment, the mortality of PCa remained in 6.7% worldwide. 1 Multiple regimens of radiotherapy are the mainstay treatment for PCa, meanwhile, radical prostatectomy, androgen deprivation therapy (ADT) and expectant management are the restrictive options.…”

Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?

“…For instance, prostate carcinogenesis and disease progression are known to be promoted by chronic inflammation [ 109 – 111 ]. Risk factors related to prostatic inflammation are frequently related to immunological, genomic and environmental factors such as physical trauma, urinary microbial infection, chemical irritation, unhealthy diet and abnormal body weight [ 112 , 113 ]. Recruitment of leukocytes, namely macrophages, lymphocytes, granulocytes and monocytes to the prostate have been observed in the prostate cancer driven inflammation responses [ 114 , 115 ].…”