The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

Author:

Gunter Jennifer H.1,Lubik Amy A.1,McKenzie Ian1,Pollak Michael2,Nelson Colleen C.1

Affiliation:

1. Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Princess Alexandra Hospital, Level 1, Building 1, Ipswich Road, Brisbane, QLD 4102, Australia

2. McGill University, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Room E-740, Montreal, QC, Canada H3T 1E2

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.

Publisher

Hindawi Limited

Subject

Urology,Obstetrics and Gynaecology

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