Wayne Tilley

Professor Wayne Tilley

Director - Dame Roma Mitchell Cancer Res Lab

Adelaide Medical School

Faculty of Health and Medical Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.


Professor Wayne Tilley is the Director of the Dame Roma Mitchell Cancer Research Laboratories (DRMCRL), Adelaide Medical School, the University of Adelaide. His research career has spanned some 40 years in Australia, the USA and the UK, and has led to international acclaim as a world expert in the field of nuclear receptors and hormonal carcinogenesis. Professor Tilley’s research has an emphasis on mechanisms of sex hormone signalling and the emergence of resistance to hormonal therapies used in the treatment of breast and prostate cancer. He is internationally recognised for discoveries on steroid hormone receptor action, in particular androgen receptor (AR) structure and function (including cloning the human androgen receptor in the late 1980’s at UT Southwestern Medical School, Dallas TX) and AR function in breast and prostate cancers. He was one of the first to describe perturbations in AR signalling critical to progression of prostate cancer, including evidence for the oncogenic potential of the AR. Most recently, his research has provided evidence that the AR is a tumour suppressor in estrogen receptor (ER)-positive breast cancer and that the progesterone receptor (PR) can inhibit ER action in human breast cancer tissues by a novel reprograming mechanism (Nature 2015). This research has led to 4 clinical trials of AR and PR activation in ER-driven disease.

Professor Tilley’s research is unique in leveraging similarities in breast and prostate cancer to forge new insights into disease mechanisms and novel treatment strategies. Research in the DRMCRL uses contemporary genomic techniques and unique patient-derived model (PDEs, PDXs) systems to gain a deeper understanding into how sex hormones and their receptors control tumour behaviour. This information is used to develop new treatment strategies, with a clear view to improving patient outcomes.

Professor Tilley’s research has attracted significant funding from government, non-government and philanthropic sources. He has published over 200 peer-reviewed papers. In 2016 he received the Endocrine Society of Australia Senior Plenary Award and gave the introductory Plenary Lecture at the 2016 International Congress of Endocrinology in Beijing, China. He was Chair of the 2015 Gordon Research Conference on Hormone-Dependent Cancers and a co-chair of the recent Fusion Nuclear Receptor Meeting in Nassau (24-17 February, 2020). Professor Tilley convenes the International PacRim Breast and Prostate Cancer Meeting Series.

 

The Dame Roma Mitchell Cancer Research Laboratories (DRMCRL) have an international reputation for research into sex hormone action in hormone-dependent cancers, with a particular emphasis on breast and prostate cancers.

This world-class cancer research centre brings together expertise spanning more than 30 years in basic and translational prostate and breast cancer research. It is the leading centre in Australia with a multidisciplinary team of scientists, clinicians and patient advocates dedicated to understanding how sex hormones and their receptors control tumour behaviour in both disease contexts. The information is used to understand mechanisms of resistance to existing hormonal therapies for breast and prostate cancer and in developing new strategies for disease treatment and management. Research programs span discovery, drug development and clinical translation.

A major research focus at the DRMCRL is the development of novel androgen receptor (AR) and progesterone receptor (PR) targeted therapies for breast and prostate cancer. In prostate cancer, this involves the generation of drugs to inhibit aberrant forms of the AR that drive the disease and are unresponsive to conventional androgen deprivation therapies. In the case of breast cancer, our research has led to new strategies to activate the AR or PR to inhibit growth of tumours that are driven by the estrogen receptor (ER), as well as interrogation of Selective Androgen Receptor Modulators (SARMs), which have the ability to reprogram oncogenic AR activation in ER negative breast cancer.

Our laboratory has pioneered integration of genomic technologies with unique preclinical models of human breast and prostate cancers, especially patient-derived explant cultures and xenograft models, to better understand disease mechanisms and facilitate translation of breast and prostate cancer research into the clinic.

We publish in high impact journals such as Nature, Nature Genetics, Nature Reviews Cancer, Cancer Research, Clinical Cancer Research and Oncogene. Our research is well supported by funding from nationally and internationally competitive grants. The DRMCRL offers students a wide array of projects that span cutting-edge biomedical research using contemporary pre-clinical models, genome-wide technologies and access to large proteomic/genomic databases.

We are currently actively seeking students interested in bioinformatics to interrogate these databases, with opportunities of cross faculty supervision in fields such as mathematics and machine learning.

 

Key Research Projects Available for DRMCRL

Project 1 - Transforming endocrine therapy for breast and prostate cancer

Description -  Breast and prostate cancers are diseases driven by abnormal sex hormone receptor activity mediated by the estrogen receptor (ER) in breast and the androgen receptor (AR) in prostate cancers. Surgery and radiation therapy for these diseases work well when the tumour is confined within the organ of origin. However, for cancers that have spread out of the breast or prostate, either locally or to other parts of the body, the major treatment strategy is to completely abolish the activity of the offending sex hormone receptor. This treatment strategy is called hormone deprivation therapy and has been employed for the past century. Overwhelming evidence indicates that hormone deprivation therapy has run its course in providing a survival advantage to people with breast or prostate cancer.

Our hypothesis is that reprogramming estrogen or androgen receptors (ER and AR) away from oncogenic activity toward more benign activity will transform endocrine therapy for breast and prostate cancer. In this project we aim to discover optimal strategies to reprogram ER or AR activity in breast and prostate cancer by investigating three complementary approaches to reprogramming ER/AR: 1) Activate other nuclear receptors that directly inhibit ER/AR signalling; 2) Utilize selective ER/AR ligands; and 3) Enhance ER/AR reprogramming with epigenetic drugs. We will then validate optimal reprogramming strategies in patient-derived xenograft “clinical trials” and clinical samples.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2022

 

Project 2 - Selective activation of androgen receptor to treat estrogen receptor positive breast cancer

Description - Androgens, acting via the androgen receptor (AR), a protein related to the estrogen receptor (ER), are natural inhibitors of estrogen-stimulated breast cancer growth. Although androgens are commonly considered to be male hormones, females produce androgens throughout their life. AR typically is present in the same cells as ER, resulting in estrogen and androgen hormones exerting opposing forces on the growth of ER-positive breast cancers, with estrogen having growth promoting and androgens protective effects.

The goals of this project are: 1) Investigate how stimulation of the androgen receptor (AR) by a synthetic androgen which has been shown to be well tolerated by women, inhibits the growth of estrogen-sensitive breast tumours; and 2)  Develop and evaluate proteins identified as being potential biomarkers of response to androgenic therapies.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2022

 

Project 3 -  The clinical significance of sex hormone crosstalk in estrogen receptor positive breast cancer

Description - Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth via the estrogen receptor (ER). We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This project will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.

In this project, we will investigate the three-way interplay between ER, PR (progesterone receptor) and AR (androgen receptor) in contemporary models of breast cancer including patient derived xenografts and ex-vivo cultured primary tumour tissues. The ultimate goal is to determine clinical scenarios in which PR, AR or both could be optimally therapeutically targeted to treat ER+ breast cancer, particularly disease resistant to current ER targeting drugs.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2022

 

Project 4 - Pushing AR toward better outcomes in breast and prostate cancers

Description - This project will establish the efficacy of drugs called SARMs (selective androgen receptor modulators) for re-activating the normal, non-oncogenic function of the AR (androgen receptor) in human-derived pre-clinical models and clinical samples of breast and prostate cancers. Currently available SARMs (eg Enobosarm) have excellent safety profiles, and are poised for rapid implementation into clinical trials. Through our collaborations with clinicians that currently run breast cancer and prostate cancer clinical trials, we have access to breast cancer and prostate cancer samples, and also an avenue to prepare them to quickly implement novel treatment strategies that arise from this project.

The aims of this project are: 1) Identify SARMs that reprogram AR from oncogenic to benign genomic loci in breast cancers and prostate cancers; 2) Identify proteins that mediate AR reprogramming in breast and prostate cancers; 3) Pre-clinically test selected SARMs with therapeutic potential; and 4) Determine the clinical scope for SARMs and candidate biomarkers derived during the project. 

Available for: Honours and HDR

Start Date: Semester 1 and 2 2022

 

Project 5 - Targeting CDK9 in triple negative and endocrine-resistant breast cancers

Description - Triple negative breast cancer (TNBC) is the worst form of breast cancer at diagnosis. Better treatments for these cancers is a critical unmet need. TNBC preferentially afflicts young women and those with mutations of the BRCA1 gene. Another very aggressive form of breast cancer is estrogen receptor (ER) driven cancer that becomes resistant to ER targeting therapies. Chemotherapy and more recently, CDK4/6 inhibitors are the only approved means of treating these cancers, but survival rates remain low.

This project focuses on these highly aggressive breast cancers that collectively cause the majority of breast cancer-related death.  Such cancers have phenomenal rates of growth, in part due to elevated transcriptional activation of oncogenes. In collaboration with a medicinal chemist (Prof Shudong Wang), we are testing new drugs that specifically target CDK9, a factor that can ramp up the transcriptional activity of RNA polymerase II.  The goals of this project are: 1) Demonstrate the efficacy of novel CDK9 inhibitors in a unique suite of patient-derived xenograft models of triple negative and endocrine-resistant breast cancer; 2) Identify cellular mediators of CDK9-targeted therapy in these disease subtypes; and 3) Test our CDK9 inhibitors in prospectively-collected patient derived explant tumours cultured ex vivo and evaluate a biomarker signature of treatment response.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2022

 

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  • Appointments

    Date Position Institution name
    2014 Visiting Professorship University of Turku
    2012 - 2014 Visiting Scientist, Cancer Research UK Cambridge University
    2006 Co-Director Adelaide Prostate Cancer Research Centre
    2002 Director, Dame Roma Mitchell Cancer Research Laboratories The University of Adelaide
    2001 - 2002 Visiting Fellow, Norris Comprehensive Cancer Center University of Southern California
    1996 - 2001 Director, Flinders Cancer Centre Flinders University
    1992 - 1998 NHMRC Senior Research Fellow Flinders University
    1991 - 1992 NHMRC CJ Martin Fellow Flinders University
    1989 - 1991 Visiting Fellow, Department of Internal Medicine University of Texas Southwestern Medical Center
    1987 - 1989 NHMRC CJ Martin Fellow University of Texas Southwestern Medical Center
    1983 - 1986 NHMRC Senior Research Officer, Department of Surgery Flinders University
  • Awards and Achievements

    Date Type Title Institution Name Country Amount
    2016 Award 2016 Senior Plenary Award Endocrine Society of Australia Australia
    2015 Award Executive Dean’s Awards 2015 The University of Adelaide Australia
    2008 Award Ron Ross Award 4th PacRim Breast and Prostate Cancer Meeting Canada
  • Education

    Date Institution name Country Title
    1984 Flinders University of South Australia Australia PhD
    1976 University of Adelaide Australia B. Sc (Hons)
  • Postgraduate Training

    Date Title Institution Country
    1987 - 1989 NHMRC CJ Martin Fellow University of Texas Southwestern Medical Center at Dallas United States
  • Research Interests

NHMRC Ideas Grant

APP1186647

2020-2023

$1,148,310

A combinatorial drug strategy to target lethal forms of breast cancer.

W.D. Tilley, E. Lim, R. Iggo, J. Carroll

NHMRC Project Grant

APP1145777

2018-2021

$998,754

Pushing AR toward better outcomes in breast and prostate cancers.

W.D. Tilley, T. Hickey, L. Selth, J. Carroll, E. Lim, W. Zwart, A. Joshua, C. Sweeney

NHMRC Project Grant  APP1138242

2018-2021

$799,440

A novel strategy for targeting castrate-resistant prostate cancer.

G. Risbridger, W.D. Tilley, L. Furic, S. Sandhu, A. Azad, L. Selth, M. Lawrence

Movember and National Breast Cancer Foundation, Australia

2018-2021

$2,958,714

Transforming endocrine therapy for breast and prostate cancer.

W.D. Tilley, G. Risbridger, J. Carroll, E. Lim, S. Clark, T. Hickey, L. Selth  

The Hospital Research Foundation, Australia

2018-2021

$375,000.00

Transforming therapy for breast and prostate cancer.

W.D. Tilley, T. Hickey, L. Selth

NHMRC Development Grant

APP1135682

2018-2020

$1,171,199

Development of a novel and highly selective CDK4/6 inhibitor for treating cancer.

S. Wang, R. Milne, W.D. Tilley, E. Lim

Cancer Research UK, Cambridge University

A23654

2018-2020

£193,783

PEARL Study: A window of opportunity study to assess the biological effects of progesterone in premenopausal ER-positive, PgR-positive early breast cancer.

C. Palmieri, W.D. Tilley, S. Chauhan, C. Rawcliffe, J. Neoptolemos, J. Carroll, E. Lim

NHMRC Project Grant APP1121057

2017-2020

$959,423

Dual targeting of the Androgen Receptor for Effective and Durable Control of Lethal Prostate Cancer.

W.D. Tilley,  G. Risbridger,  G. Raj,  L. Selth,  J. Taylor,  A. Joshua

NHMRC Project Grant

APP1130077

2017-2020

$1,023,132

The clinical significance of sex hormone receptor crosstalk in ER+ breast cancer.

W.D. Tilley, J. Carroll, T. Hickey, E. Lim, L. Selth, E. Ebrahimie, S. Birrell, C. Palmieri, G. Greene, A. Bruna, C. Lange, F. Classens, N. Dean, F. Markowetz, A. Swarbrick

Cancer Council of NSW

2017-2019

$450,000

WinPro: Progesterone as an anticancer therapy in early breast cancer.

E. Lim, W.D. Tilley

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  • Current Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2020 Co-Supervisor Network-based approaches for integration of multi-omic data in hormone-dependent cancers Master of Philosophy (Medical Science) Master Full Time Miss Wenjun Liu
    2019 Co-Supervisor Elucidating the Interplay Between Androgen Receptor Signalling and Lipid Metabolism in Prostate Cancer Doctor of Philosophy Doctorate Full Time Ms Meiwen Danielle Fang
    2017 Co-Supervisor Role of the GATA3 transcription factor on AR signalling In ER-positive breast cancer Doctor of Philosophy Doctorate Full Time Mrs Leila HosseinZadeh
    2017 Co-Supervisor Interactions between Androgen signalling and the lipid microenvironment in prostate cancer Doctor of Philosophy Doctorate Full Time Mr Raj Kumar Shrestha
    2017 Co-Supervisor Androgen receptor co-regulators mediating the actions of selective androgen receptor modulators and dihydrotestosteron in TNBC Doctor of Philosophy Doctorate Full Time Mrs Ebtihal Hashem Mustafa
    2017 Co-Supervisor Development of Microfluidic Technology for Genomic Studies of Circulation Tumor Cells Doctor of Philosophy Doctorate Full Time Mr Mohammadreza Alizadeh Ghodsi
  • Past Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2016 - 2020 Co-Supervisor The Role of MicroRNA-194 in Prostate Cancer Progression Doctor of Philosophy Doctorate Full Time Miss Rayzel Candida Fernandes
    2010 - 2016 Co-Supervisor The Role of Estrogen Receptor and the Androgen Receptor in Human Breast Cancer Doctor of Philosophy Doctorate Part Time Mrs Shalini Jindal
    2009 - 2013 Co-Supervisor Investigation into the Expression and Localisation of C-Kit and the Regulation of Kit Ligand Gene Expression in the Adult Human Ovary Doctor of Philosophy Doctorate Full Time Dr Astrud Tuck
    2008 - 2012 Co-Supervisor The Molecular Actions of Medroxyprogesterone Acetate on Androgen Receptor Signalling and the Promotion of Breast Cancer Doctor of Philosophy Doctorate Full Time Miss Aleksandra Ochnik
    2008 - 2011 Co-Supervisor Characterisation of the Co-chaperone Small Glutamine-rich Tetratricopeptide Repeat containing Protein Alpha as a Regulator of Androgen Receptor Activity in Prostate Cancer Cells Doctor of Philosophy Doctorate Full Time Dr Andrew Trotta
    2008 - 2012 Co-Supervisor The Role of Small Glutamine-Rich Tetratricopeptide Repeat Containing Protein Alpha in Female Reproductive Tissues Doctor of Philosophy Doctorate Full Time Ms Miriam Simone Butler
    2007 - 2012 Co-Supervisor Mathematical Models of Cell Cycle Progression: Applications to Breast Cancer Cell Lines Doctor of Philosophy Doctorate Part Time Miss Kate Simms
    2007 - 2015 Co-Supervisor Combinatorial Targeting of the Androgen Receptor for Prostate Cancer Therapy Doctor of Philosophy Doctorate Full Time Miss Sarah Carter
    2006 - 2010 Co-Supervisor The Role of Epigenetic Modifications in Prostate Tumourigenesis Doctor of Philosophy Doctorate Full Time Ms Karen Huiqin Chiam
    2004 - 2008 Co-Supervisor Characterisation of a Dominant Negative Androgen Receptor in Prostate Cancer Cells Doctor of Philosophy Doctorate Part Time Dr Margaret Centenera
    2004 - 2008 Co-Supervisor Androgen Signalling in Normal and Malignant Breast Epithelial Cells Doctor of Philosophy Doctorate Part Time Ms Amelia Peters
    2004 - 2008 Co-Supervisor Androgens and Androgen Receptor Signalling in Men Doctor of Philosophy Doctorate Full Time Dr Eleanor Need
    2003 - 2007 Principal Supervisor Targeting the Androgen Receptor as a Therapeutic Strategy for Prostate Cancer Doctor of Philosophy Doctorate Full Time Miss Deborah Marrocco
    2002 - 2004 Co-Supervisor Versican: regulation, purification, and biological properties of a candidate prognostic indicator for breast cancer Doctor of Philosophy Doctorate Full Time Miss Supaporn Suwiwat
    2002 - 2004 Principal Supervisor ANDROGEN SIGNALLING IN HUMAN BREAST CANCER CELLS Doctor of Philosophy Doctorate Full Time Dr Nicole Moore
  • Other Supervision Activities

    Date Role Research Topic Location Program Supervision Type Student Load Student Name
    2021 - ongoing Principal Supervisor Exploring the role of steroid receptors in ER+ breast cancer. University of Adelaide Doctor of Philosophy (Medical Science) Doctorate Full Time Alex Pace
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  • Industry Partnerships

    Date Engagement Type Partner Name
    2019 - ongoing Consultant Radius Health, Waltham, Massachusetts: Selective androgen receptor modulators (SARMs) and breast cancer program.
  • Review, Assessment, Editorial and Advice

    Date Title Type Institution Country
    2008 - ongoing Advisory Editor Journal Review Endocrine-Related Cancer
    2008 - ongoing Editorial Board Journal Review Oncology Times
  • Position: Director - Dame Roma Mitchell Cancer Res Lab
  • Phone: 83137861
  • Email: wayne.tilley@adelaide.edu.au
  • Campus: North Terrace
  • Building: Adelaide Health and Medical Sciences, floor 8
  • Room: WS8060.01
  • Org Unit: Medical Specialties

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