Prostate cancer: from the pathophysiologic implications of some genetic risk factors to translation in personalized cancer treatments

Abstract

Several pathologies affect human prostate, such as prostate cancer (PC), which is the most common non-skin malignant cancer in Western male populations. A complex interaction between genetic and environmental factors (i.e. infectious agents, dietary carcinogens) and hormonal imbalances has been reported to have a fundamental role in PC pathophysiology by evoking chronic inflammation. Thus, chronic inflammation drives prostate carcinogenesis and neoplastic progression. No adequate biomarkers exist until now to guide PC prognosis and treatment. Accordingly, the research has particularly focused its attention on genetic variants in genes, codifying molecules of signaling innate immune/inflammatory and steroid metabolism pathways, which are able to modify the PC genetic susceptibility and clinical disease outcome. Single-nucleotide polymorphisms (SNPs) may operate in combination to create a 'risk profile'. Combinations of several inflammatory and sex steroid hormone pathway SNPs are found in PC patients. Thus, their combinations might be used as promising biomarkers in a pre- and post-treatment clinical PC setting. Indeed, their identification may hold promise for the realization of a personalized PC medicine. Many of these aspects are summarized in this report through the elucidation of literature data and the results of our studies.

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

“…In complex, these literature data suggest that the TLR-4 pathway should seem to have a crucial role in sporadic TAA patho-physiology and represent a crucial link between pathways linked to sporadic TAA development and immune system, as suggested in our reports [33,50,[52][53][54][55]. However, this encouraging and increasing evidence is fruit prevalently of animal investigations.…”

“…As above mentioned, it has been suggested that TLR-4 pathway has a key role in the pathophysiology of several CVDs [50,[52][53][54][55]. Recently, the group of Pasterkamp has provided an overview of the endogenous molecules, released under cellular cardiovascular stress and damage, the DAMPs, which can trigger innate immunity via TLR-4-mediated signaling pathway and induce CVD onset as consequence [52].…”

“…Recently, the group of Pasterkamp has provided an overview of the endogenous molecules, released under cellular cardiovascular stress and damage, the DAMPs, which can trigger innate immunity via TLR-4-mediated signaling pathway and induce CVD onset as consequence [52]. In addition, polymorphisms of TLR-4 gene (MIM: 603030), and particularly the rs4986790 TLR-4 polymorphism, have been associated with the risk of several CVDs and other age-related diseases, even if contrasting results have been reported in literature [33,50,[52][53][54][55].…”

A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA

“…Common treatments for prostate cancer such as surgery, hormone therapy, radiation therapy, and chemotherapy have been commonly used for PCa treatments [1,2]. Alternative therapeutic modalities such as targeted therapy with cancer specificity would be a better treatment to enhance therapeutic efficacy in prostate cancer patients.…”

Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis

“…In particular, several studies have suggested that sexually transmitted infections may be a risk factor for PCa through causing inflammation, even though not all the studies are consistent [7], [8]. Chronic inflammation seems to induce prostate carcinogenesis and also promote neoplastic progression [9]. Furthermore, several pathways linking inflammation and PCa have been identified: an intrinsic one driven by genetic events that cause neoplasia, and an extrinsic one driven by inflammatory conditions that predispose to cancer [9].…”