556 Antagonizing microRNA mediated epigenetic reprogramming as therapeutic strategy for aggressive prostate cancer

: Prostate Cancer (PC) is one the most prominent cause of deaths in males worldwide especially in western countries. The exhaustive research into prostate cancer to date has demonstrated ELAC2, RNASEL, MSR1, NBS1, CHEK2, MYC, BCL-2, c-Kit, tumor suppressor genes, BRCA1, BRCA2, PACE4, GSTP1, PTEN,CDKN1B, NKX3.1, KLF6, FOXA1, Retinoblastoma, p53, androgen receptor, kallikreins, ETS, CYP17, SRD5A2, E-cadherin, KAI1/CD82, hepsin, AMACR, PIM1, MTA-1, EZH2, EPHB2, growth factors & its receptors, cannabinoid receptors, annexins, oxidative stress and inflammation are entailed changes underlying the initiation, development, and progression of PC. Furthermore, oncology would shift from a reactive to proactive discipline so exploring these targets open new area of research. Therefore, the present review is focused on molecular pathophysiology biomarkers for the progression of PC that would encourage the researchers and pharmaceutical industries to investigate potential therapeutic strategy to overcome demerits of currently available clinically therapies.

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Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer

Cancers ◽

10.3390/cancers13071495 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1495

Author(s):

Tú Nguyen-Dumont ◽

James G. Dowty ◽

Robert J. MacInnis ◽

Jason A. Steen ◽

Moeen Riaz ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Prediction ◽

Prediction Models ◽

Risk Prediction Models ◽

Aggressive Prostate Cancer ◽

Panel Testing ◽

Pathogenic Variants ◽

Increased Risk ◽

Predisposition Genes ◽

Rare Genetic Variants

While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p < 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7–12.4)), BRCA1 (5.5 (1.8–16.6)), and ATM (3.8 (1.6–9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.

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