Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review

被引:13
作者
Karunasinghe, Nishi [1 ]
Masters, Jonathan [2 ]
Flanagan, Jack U. [1 ]
Ferguson, Lynnette R. [1 ,3 ]
机构
[1] Univ Auckland, FM&HS, Auckland Canc Soc Res Ctr, Private Bag 92019, Auckland 1142, New Zealand
[2] Auckland Hosp, Urol Dept, Auckland, New Zealand
[3] Univ Auckland, FM&HS, Discipline Nutr & Dietet, Auckland, New Zealand
关键词
AKR1C3; rs12529; extra-testicular androgen; prostate-specific antigen (PSA); prostate cancer (PC); cancer progression; androgen deprivation therapy (ADT); inhibitors; 5 17-BETA-HYDROXYSTEROID-DEHYDROGENASE AKR1C3; ANDROGEN-DEPRIVATION THERAPY; TYPE-3 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE; STEROIDOGENIC ENZYME AKR1C3; 1 MEMBER C3; ADIPOSE-TISSUE; IN-VITRO; SELECTIVE INHIBITORS; INTRATUMORAL STEROIDOGENESIS; INCREASED EXPRESSION;
D O I
10.2174/1568009617666170330115722
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that are involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes. This review brings together information with regards to key functions of this enzyme, its relevance in PC, its transcriptional regulation, clinical aspects associated with genetics, differential regulation in cancer and cancer progression, and the types of AKR1C3 inhibitors with future therapeutic value. Conclusion: Based on these discussions, hypotheses are forwarded for future applicability of this enzyme and its genetic variants in transformational medical practices in PC. Options for the use of personalised AKR1C3 inhibitor drugs for late stage PC are also discussed.
引用
收藏
页码:603 / 616
页数:14
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