Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142. New Zealand.
Urology Department, Auckland Hospital, Auckland. New Zealand.
Curr Cancer Drug Targets. 2017;17(7):603-616. doi: 10.2174/1568009617666170330115722.
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.
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.
醛酮还原酶 1C3(AKR1C3)是一种具有多种底物的重要氧化还原酶,参与产生睾丸外雄激素。其活性受环境暴露以及遗传变异的影响。这些遗传变异可能导致睾酮水平的变化,进而影响雄激素受体(AR)的激活。这可能导致前列腺特异性抗原(PSA)的下游产物产生差异。由于 PSA 水平用于前列腺的临床评估,这些变化可能会影响前列腺癌(PC)的诊断以及 PC 管理的结果。本综述汇集了有关该酶的关键功能、其在 PC 中的相关性、转录调控、与遗传相关的临床方面、在癌症和癌症进展中的差异调控以及具有未来治疗价值的 AKR1C3 抑制剂类型的信息。
基于这些讨论,提出了该酶及其遗传变异在 PC 转化医学实践中的未来适用性的假设。还讨论了使用个性化 AKR1C3 抑制剂药物治疗晚期 PC 的选择。