title: The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer.
abstract: An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Princess Alexandra Hospital, Level 1, Building 1, Ipswich Road, Brisbane, QLD 4102, Australia.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Gunter
authors.forename: Amy A
authors.initials: AA
authors.lastname: Lubik
authors.forename: Ian
authors.initials: I
authors.lastname: McKenzie
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson