Prostate Cancer Research Group Leader, ARC Future Fellow
Bachelor of Science, University of Adelaide
Bachelor of Science (Hons), University of Adelaide
Doctor of Philosophy (Medicine), University of Adelaide
I head a translational research program focussed on development of more effective diagnostic markers and targeted therapies for prostate cancer, encompassing preclinical bench research through to clinical trials. My work on novel classes of drugs that target androgen receptor signalling and Heat Shock Protein 90 are improving our understanding of individual drug responses in prostate cancer patients.
I have also recently been granted a Movember Revolutionary Team Award to investigate the role of lipid metabolism in prostate cancer, which has the potential to improve diagnosis and treatment options. Underpinning this research program has been the development of better pre-clinical models of disease using tissues donated from prostate cancer patients, which will greatly improve the “strike rate” for translating new therapies from the laboratory to the clinic.
59 journal articles and 3 book chapters published since 1997. Publications since 2010 include:
- Butler LM, Ferraldeschi R,Armstrong HK, Centenera MM and Workman P.Maximizing the Therapeutic Potential of Hsp90 Inhibitors. Mol Cancer Res. In press 2015.
- Centenera MM, Carter SL, Gillis JL, Marrocco-Tallarigo DL, Grose RH, Tilley WD and Butler LM. Co-targeting AR and HSP90 suppresses prostate cancer cell growth and prevents resistance mechanisms. Endocr Relat Cancer. pii: ERC-14-0541. In press, 2015.
- Johnson IR, Parkinson-Lawrence EJ, Butler LM and Brooks DA. Prostate cell lines as models for biomarker discovery: performance of current markers and the search for new biomarkers. Prostate 74: 547-560, 2014.
- Rodrigues DN, Butler LM, Estelles DL and de Bono JS. Molecular pathology and prostate cancer therapeutics: from biology to bedside. J Pathol 232: 178-184, 2014.
- Bianco-Miotto T, Trotta A, Need EF, Lee AM, Ochnik AM, Giorgio L, Leach DA, Swinsetad EE, O’Loughlin MA, Newman MR, Birrell SN, Butler LM, Harris JM and Buchanan G. Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and D(4)-tibolone. Mol Cell Endocrinol 382: 899-908, 2014.
- Selth LA, Roberts MJ, Chow CW, Marshall VR, Doi SA, Vincent AD, Butler LM, Lavin MF, Tilley WD and Gardiner F. Human seminal fluid as a source of prostate cancer specific microRNA biomarkers. Endocr Relat Cancer 21:L17-21, 2014.
- Tarulli G, Butler LM, Tilley WD and Hickey TE. Bringing androgens up a notch in breast cancer. Endocr Relat Cancer 21:T183-202, 2014.
- Ochnik AO, Moore NL, Jankovic-Karasoulos T, Bianco-Miotto T, Ryan NK, Thomas MR, Birrell SN, Butler LM, Tilley WD and Hickey TE. The anti-androgenic actions of medroxyprogesterone acetate in epithelial cells within normal human breast tissues cultured ex vivo. Menopause 21: 79-88, 2014.
- Johnson IR, Parkinson-Lawrence EJ, Shandala T, Weigert R, Butler LM and Brooks DA. Altered Endosome Biogenesis in Prostate Cancer has Biomarker Potential. Mol Cancer Res 12:1851-62, 2014.
- Moore NL, Centenera MM, Butler LM, Hickey TE and Tilley WD. Androgen and AR. IN: Gelmann E & Sawyers CL (Eds) Molecular Oncology: causes of cancer and targets for treatment. Chapter 32:378-391. Cambridge University Press, New York, 2014.
- Selth LA, Townley SL, Gillis JL, Tilley WD and Butler LM. Identification of prostate cancer-associated microRNA in circulation using a mouse model of disease. Method Mol Biol 1024: 235-246, 2013.
- Comstock CES, Augello MA, Goodwin JF, de Leeuw R, Schiewer MJ, Ostrander Jr. WF, Burkhart RA, McClendon KA, McCue PA, Trabulsi EJ, Lallas CD, Gomella LG, Centenera MM, Brody JR, Butler LM, Tilley WD and Knudsen KE. Targeting cell cycle and hormone receptor pathways in cancer. Oncogene 32: 5481-5491, 2013.
- Abankwa D, Millard SM, Martel N, Choong CS, Yang M, Butler LM, Buchanan G, Tilley WD, Ueki N, Hayman MJ and Leong GM. Ski-interacting protein (SKIP) interacts with androgen receptor in the nucleus and modulates androgen-dependent transcription. BMC Biochem. 14:10, 2013.
- Philp LK, Butler MS, Hickey TE, Butler LM, Tilley WD and Day TK. SGTA: a new player in the molecular co-chaperone game. Horm Cancer 4: 343-357, 2013.
- Ravindranathan P, Lee TK, Yang L, Centenera MM, Butler L, Tilley WD, Hsieh JT, Ahn JM and Raj GV. Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer. Nat Commun 4: 1923, 2013.
- Trotta AP, Need EF, Selth LA, Chopra S, Pinnock CB, Lech DA, Coetzee GA, Butler LM, Tilley WD and Buchanan G. Knockdown of the cochaperone GTA results in the suppression of androgen and PI3K/Akt signaling and inhibition of prostate cancer cell proliferation. Int J Cancer 133: 2812-2823, 2013.
- Centenera MM, Fitzpatrick A, Tilley WD and Butler LM. Hsp90: Still a viable target in prostate cancer. BBA-Rev Cancer 1835: 211-218, 2013.
- Centenera MM, Raj GV, Knudsen KE, Tilley WD and Butler LM. Ex vivo culture of human prostate tissue and drug development. Nat Rev Urol. 10:483-487, 2013.
- Gillis JL, Selth LA, Centenera MM, Townley SL, Sun S, Plymate SR, Tilley WD and Butler LM. Constitutively-active androgen receptor variants function independently of the HSP90 chaperone but do not confer resistance to HSP90 inhibitors. Oncotarget 4: 691-704, 2013
- Selth LA, Townley SL, Bert A, Stricker P, Sutherland P, Horvath LJ, Goodall GA, Butler LM and Tilley WD. Circulating microRNAs predict biochemical recurrence in prostate cancer patients. Br J Cancer 109: 641-650, 2013.
- Chiam K, Ryan NK, Ricciardelli C, Day TK, Buchanan G, Ochnik AM, Murti K, Selth LA, Australian Prostate Cancer BioResource, Butler LM, Tilley WD and Bianco-Miotto T. Characterization of the prostate cancer susceptibility gene KLF6 in human and mouse prostate cancers. Prostate 73:182-93, 2013.
- Dean JL, McClendon AK, Hickey TE, Butler LM, Tilley WD, Witkiewicz AK and Knudsen ES. Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors. Cell Cycle 11:2756-61, 2012.
- Trotta A, Need EN, Butler LM, Selth LA, O’Loughlin MA, Coetzee GA, Tilley WD and Buchanan G. Subdomain structure of the co-chaperone SGTA and activity of its androgen receptor client. J Mol Endocrinol 49: 57-68, 2012.
- Betterman KL, Paquet-Fifield S, Asselin-Labat ML, Visvader JE, Butler LM, Stacker SA, Achen MG and Harvey NL. Remodeling of the lymphatic vasculature during mouse mammary gland morphogenesis is mediated via epithelial derived lymphangiogenic stimuli. Am J Pathol 181:2225-38, 2012.
- Moore NL, Buchanan G, Harris JM, Selth LA, Bianco-Miotto T, Hanson AR, Birrell SN, Butler LM, Hickey TE and Tilley WD. An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity. Endocr Rel Cancer 19: 599-613, 2012.
- Centenera MM, Gillis JL, Hanson A, Jindal S, Taylor RA, Risbridger GP, Sutherland PD, Scher HI, Raj GV, Knudsen KE, Yeadon T for the Australian Prostate Cancer BioResource, Tilley WD and Butler LM. Evidence for efficacy of new Hsp90 inhibitors revealed by ex vivo culture of human prostate tumors. Clin Cancer Res 18: 3562-3570, 2012- featured in Highlights section of Nat Rev Urol 9, 356 (July 2012).
- Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, Liu F, Planck JL, Ravindranathan P, Chinnaiyan AM, McCue P, Gomella LG, Raj GV, Dicker AP, Brody JR, Pascal JM, Centenera MM, Butler LM, Tilley WD, Feng FY and Knudsen KE. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov 2:1134-1149, 2012.
- Selth LA, Townley S, Gillis JL, Ochnik A, MacFarlane R, Chi K, Murti K, Marshall VR, Tilley WD and Butler LM. Discovery of circulating microRNAs associated with prostate cancer using a mouse model of disease. Int J Cancer 131:652-61, 2012.
- Selth LA, Tilley WD and Butler LM. Circulating microRNAs– macro-utility as markers of prostate cancer? Endocr Relat Cancer 19: R99-R113, 2012.
- Moore NL, Hickey TE, Butler LM and Tilley WD. Multiple nuclear receptor signaling pathways mediate the actions of synthetic progestins in target cells. Mol Cell Endocrinol 357: 60-70, 2012.
- Thompson VC, Day TK, Bianco-Miotto T, Selth LA, Han G, Thomas M, Buchanan G, Scher HI, Nelson CC, the Australian Prostate Cancer BioResource, Greenberg NM, Butler LM and Tilley WD. A gene signature identified using a mouse model of androgen receptor-dependent prostate cancer predicts biochemical relapse in human disease. Int J Cancer 131: 662-672, 2012.
- Chiam K, Centenera MM, Tilley WD, Butler LM and Bianco-Miotto T. GSTP1 DNA methylation and expression status is indicative of 5-aza-2'-deoxycytidine efficacy in human prostate cancer cells. PLoS One 6:e25634, 2011.
- Peters AA, Ingman WJ, Tilley WD and Butler LM. Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and post-pubertal murine mammary gland. Endocrinology 152:3728-37, 2011.
- Buchanan G, Need EF, Barrett JM, Bianco-Miotto T, Thompson VC, Butler LM, Marshall VR, Tilley WD and Coetzee GA. Corepressor effect on androgen receptor activity varies with the length of the CAG encoded polyglutamine repeat and is dependent on receptor/corepressor ratio in prostate cancer cells. Mol Cell Endocrinol 342:20-31, 2011.
- Bianco-Miotto T, Chiam K, Buchanan G, Jindal S, Day TK, Thomas M, Pickering MA, O'Loughlin MA, Ryan NK, Raymond WA, Horvath LG, Kench JG, Stricker PD, Marshall VR, Sutherland RL, Henshall SM, Gerald WL, Scher HI, Risbridger GP, Clements JA, Butler LM, Tilley WD, Horsfall DJ, Ricciardelli C; Australian Prostate Cancer BioResource. Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol Biomarkers Prev. 19:2611-2622, 2010.
Recipient of 4 research fellowship and 26 research grants since 2003. Grants awarded since 2010 include:
- Butler LM, Daly R, Tilley WD, Horvath LG and Centenera MM. Molecular hallmarks of heat shock protein 90 inhibition in prostate cancer. Cancer Australia, 2015-2017; $562,030.
- Butler LM, Swinnen JV, Tilley WD, Scott AM, Hoy AJ and Wittert GA. Exploiting alterations in lipid metabolism to improve diagnosis, treatment and molecular imaging of prostate cancer. Movember Foundation / Prostate Cancer Foundation of Australia, 2015-2017; $3,250,000.
- Butler LM. Research Fellowship: Molecular hallmarks of androgen receptor targeting in prostate cancer. Australian Research Council Future Fellowship, 2013-2016; $846,240.
- Butler LM, Horvath LJ, Tilley WD, Stocker M, Stricker PD and Kench JD. A pharmacodynamic study of the heat shock protein 90 (Hsp90) inhibitor, AUY922, in high-risk, localised prostate cancer. Cancer Australia, 2013-2015; $590,408.
- Tilley WD, Butler LM, Plymate S and Selth LA. Mechanism and targeting of castration resistant prostate cancer. Cancer Australia, 2013-2015; $586,398.
- Centenera MM and Butler LM. Evaluation of biomarkers of response to Hsp90 inhibition in human prostate cancer. Royal Adelaide Hospital Clinical Research Grant, 2013; $48,000.
- Butler LM, Brook N, Sutherland P and Saunders P. Development of an Australian prostate cancer reference cohort to support research identifying better biomarkers that predict disease progression. Royal Adelaide Hospital Clinical Research Grant, 2013; $18,000.
- Butler LM, Centenera MM, Claessens F and Swinnen JV. Exploiting metabolic alterations to more accurately monitor prostate cancer therapy. Prostate Cancer Foundation of Australia, 2012-2013; $299,817.
- Tilley WD, Butler LM, Hoffman P, Goodall G and Scher H. A novel approach to predict metastatic potential at prostate cancer diagnosis. Cancer Australia (Priority Driven Collaborative Cancer Research Scheme), 2011-2013; $591,732.
- Buchanan G, Kee T and Butler LM. Targeting chemokine signalling in prostate cancer. Prostate Cancer Foundation of Australia, 2011-2012; $250,000.
- Butler LM, Tilley WD and Scher HI. A combinatorial approach targeting androgen signalling for treatment of prostate cancer. Prostate Cancer Foundation of Australia/Cancer Australia, 2010-2012; $589,673.
- Tilley WD, Butler LM, Scher H and Bianco-Miotto T. The essential role of androgen receptor signalling in prostate tumorigenesis. NHMRC, 2010-2012; $813,913.
- Centenera MM, Butler LM and Tilley WD. Identification of biomarkers of response to Hsp90 inhibition in human prostate cancer. RAH/IMVS Research Committee, 2011; $20,000.