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 |
| Lisa Philp | 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 |
