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Grants

Revolutionary Team Award - Adaptive Response to Targeting the Androgen Axis: A Strategic Offensive on Resistance

Androgens, male sex hormones, regulate biological pathways promote growth and survival of prostate cancer. Androgen Deprivation Therapy (ADT) exploits this dependence in the treatment of advanced prostate cancer, often augmented by a growing list of additional inhibitors that target the action of androgens. 

Although targeting the androgen axis has clear therapeutic benefit in advanced prostate cancer patients, it is temporary, as prostate tumour cells adapt to survive and become resistant to subsequent treatments.  This research program hypothesises that the ultimate failure of androgen targeted therapies results from the predictable adaptive biological pathways activated in response to inhibiting androgens.   ADT and its variations induce features of metabolic syndrome, including increases in potent metabolic hormones including insulin and other hormones which promote tumour growth and spread. The tumour environment in bone is also altered by androgen targeting in a manner that may facilitate tumour growth. Removal of androgens makes prostate cancer cells “plastic” enabling them to take on features of more primitive cells such as increased ability to migrate or resistance to therapies. By defining these therapy induced changes we will be able to design new interventions to improve outcomes for men with advanced prostate cancer.

The ultimate goal of this research program is to capitalise on adaptive pathways activated by inhibition of the androgen axis to identify and strategically develop drugs to be used in combination or in sequence with androgen targeted therapies to improve outcomes in advanced prostate cancer.

Investigators

Colleen Nelson APCRC-Q, IHBI, QUT, TRI
Elizabeth Williams APCRC-Q, IHBI, QUT, TRI
Marcel Dinger Garvan Institute for Medical Research, University of New South Wales
Lisa Chopin APCRC-Q, IHBI, QUT, TRI
Adrian Herington APCRC-Q, IHBI, QUT, TRI
Jeff Holst Centenary Institute & University of Sydney
Ron Quinn Eskitis Institute for Drug Discovery, Griffith University
Dietmar Hutmacher APCRC-Q, IHBI, QUT, TRI
John O'Leary
Judith Clements APCRC-Q, IHBI, QUT, TRI
Melanie Lehman APCRC-Q, IHBI, QUT, TRI
Jennifer Gunter APCRC-Q, IHBI, QUT, TRI
Mark Cowley St Vincent's Clinical School & Garvan Institute of Medical Research
Grant Buchanan Basil Hetzel Institute for Translational Research, University of Adelaide
Eleanor Need Basil Hetzel Institute for Translational Research, University of Adelaide
Ian Vela
Wayne Tilley Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide
Lisa Butler Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide
Derek Richard APCRC-Q, IHBI, QUT, TRI
Pamela Russell APCRC-Q, IHBI, QUT, TRI
Brett Hollier APCRC-Q, IHBI, QUT, TRI
Gail Risbridger Monash University
Yuzhuo (YZ) Wang Vancouver Prostate Centre, University of British Columbia
Ken O'Byrne APCRC-Q, IHBI, QUT, TRI, PAH
Martin Gleave Vancouver Prostate Centre, University of British Columbia
John Wade Florey Institute of Neuroscience and Mental Health
Paul Rennie Vancouver Prostate Centre, University of British Columbia
David Lloyd University of South Australia
Darren Fayne Trinity College Dublin
Ross Bathgate Florey Institute of Neuroscience and Mental Health
Patrick Ling APCRC-Q, IHBI, QUT, TRI
Ralph Buttyan Vancouver Prostate Centre, University of British Columbia
Qian (Kevin) Wang Centenary Institute & University of Sydney
Stephen Finn Trinity College Dublin & Irish Prostate Cancer Consortium
Artem Cherkasov Vancouver Prostate Centre, University of British Columbia
Tanja Grkovic Eskitis Institute for Drug Discovery, Griffith University
Akhter Hossain Florey Institute of Neuroscience and Mental Health
Laszlo Otvos Temple University
Martin Sadowski APCRC-Q, IHBI, QUT, TRI
Anja Rockstroh APCRC-Q, IHBI, QUT, TRI
Stephen McPherson APCRC-Q, IHBI, QUT, TRI
Gregor Tevz APCRC-Q, IHBI, QUT, TRI

Duration

2014 - 2019