title: Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142. New Zealand.
authors.forename: Nishi
authors.initials: N
authors.lastname: Karunasinghe
authors.affiliation: Urology Department, Auckland Hospital, Auckland. New Zealand.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Masters
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland. New Zealand.
authors.forename: Jack U
authors.initials: JU
authors.lastname: Flanagan
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland. New Zealand.
authors.forename: Lynnette R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D000074425:Aldo-Keto Reductase Family 1 Member C3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: D000728:Androgens; D004791:Enzyme Inhibitors; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3
keywords: ;AKR1C3 rs12529; AKR1C3 inhibitors; androgen deprivation therapy (ADT); cancer progression; extra-testicular androgen; prostate cancer (PC); prostate-specific antigen (PSA)