Title:Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review
Volume: 17
Issue: 7
Author(s): Nishi Karunasinghe*, Jonathan Masters, Jack U. Flanagan and Lynnette R. Ferguson
Affiliation:
- Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142,New Zealand
Keywords:
AKR1C3 rs12529, extra-testicular androgen, prostate-specific antigen (PSA), prostate cancer (PC), cancer progression,
androgen deprivation therapy (ADT), AKR1C3 inhibitors.
Abstract: 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.
