1.
AKR1C3 as a target in castrate resistant prostate cancer.
Adeniji, AO, Chen, M, Penning, TM
The Journal of steroid biochemistry and molecular biology. 2013;:136-49
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Abstract
Aberrant androgen receptor (AR) activation is the major driver of castrate resistant prostate cancer (CRPC). CRPC is ultimately fatal and more therapeutic agents are needed to treat this disease. Compounds that target the androgen axis by inhibiting androgen biosynthesis and or AR signaling are potential candidates for use in CRPC treatment and are currently being pursued aggressively. Aldo-keto reductase 1C3 (AKR1C3) plays a pivotal role in androgen biosynthesis within the prostate. It catalyzes the 17-ketoreduction of weak androgen precursors to give testosterone and 5α-dihydrotestosterone. AKR1C3 expression and activity has been implicated in the development of CRPC, making it a rational target. Selective inhibition of AKR1C3 will be important, however, due to the presence of closely related isoforms, AKR1C1 and AKR1C2 that are also involved in androgen inactivation. We examine the evidence that supports the vital role of AKR1C3 in CRPC and recent developments in the discovery of potent and selective AKR1C3 inhibitors. This article is part of a Special Issue entitled 'CSR 2013'.
2.
Contribution of HOGG1 Ser³²⁶Cys polymorphism to the development of prostate cancer in smokers: meta-analysis of 2779 cases and 3484 controls.
Xu, B, Tong, N, Chen, SQ, Yang, Y, Zhang, XW, Liu, J, Hu, XN, Sha, GZ, Chen, M
PloS one. 2012;(1):e30309
Abstract
The HOGG1 gene catalyzes the excision of modified bases and removal of DNA damage adducts. It may play an important role in the prevention of carcinogenesis. Ser³²⁶Cys polymorphism localizes in exon 7 of the hOGG1 gene. It takes the form of an amino acid substitution, from serine to cysteine, in codon 326. Several epidemiological association studies have been conducted on this polymorphism and its relationship with the risk of prostate cancer. However, results have been conflicting. To resolve this conflict, we conducted a meta-analysis on the association between this polymorphism and prostate cancer, taking into account race, country, sources of controls, and smoking status. A total of nine studies covering 2779 cases and 3484 controls were included in the current meta-analysis. Although no significant association was found between hOGG1 Ser³²⁶Cys polymorphism and prostate cancer susceptibility in the pooled analysis, individuals with Ser/Cys+Cys/Cys genotypes were found to have greater risk of prostate cancer if they were also smokers (OR = 2.66, 95% CI = 1.58-4.47) rather than non-smokers (OR = 2.18, 95% CI = 1.13-4.19), compared with those with Ser/Ser genotype. In conclusion, our meta-analysis demonstrates that hOGG1 Ser³²⁶Cys polymorphism is a risk factor for prostate cancer in smokers. Further studies are needed to confirm this relationship.