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Grants

Targeting leptin in prostate cancer progression; linking metabolic dysfunction and castrate resistance

Advanced prostate cancer is treated with androgen deprivation therapy (ADT), as the prostate and prostate tumours are dependent on androgens for survival. Unfortunately, ADT only offers a temporary remission and prostate tumours begin to capitalise on additional intratumoural or adrenal sources of androgens. This has led to continued development of antagonists to the androgen receptor (AR) and inhibitors of androgen synthesis to combat prostate cancer which results in extended time to progression and cancer specific survival in advanced prostate cancer patients.

 Although targeting the androgen axis has clear therapeutic benefit, it is counter balanced by concurrent responses which result in treatment resistance and increased tumour survival.

For example, a common side-effect of ADT is the induction of features of the metabolic syndrome including increased fat mass and elevated serum levels of cholesterol, insulin and leptin. These metabolic alterations are associated with the development of high grade disease and more rapid treatment failure. Leptin is a hormone that normally regulates hunger and energy balance in our brain but also affects other parts of the body and has recently been shown to promote cancer cell growth and treatment resistance. This project will investigate the role of leptin in growth and survival of prostate cancer cells and will determine whether co-treatment with a leptin receptor antagonist offers an attractive co-target in combination with anti-androgen therapies.This project will define adaptive leptin signalling in the development of castrate resistant prostate cancer and evaluate the efficacy of an inhibitor of leptin action in prolonging the time to treatment failure and cancer progression for men on androgen deprivation therapies.

Investigators

Colleen Nelson APCRC-Q, IHBI, QUT, TRI
Elizabeth Williams APCRC-Q, IHBI, QUT, TRI
Brett Hollier APCRC-Q, IHBI, QUT, TRI
Jennifer Gunter APCRC-Q, IHBI, QUT, TRI
Martin Sadowski APCRC-Q, IHBI, QUT, TRI
Laszlo Otvos
John O'Leary

Duration

2014 - 2015

Funding

Princess Alexandra Research Foundation It's  A Bloke's Thing Prostate Cancer Research Grant $300 000