Brain Tumour Biology and Therapies

Research Overview

The research program undertaken in the Department of Surgery focuses on the biology and treatment of gliomas, the most common form of brain tumour and unfortunately, the deadliest. Grade IV glioma (glioblastoma multiforme or GBM) is the most aggressive of all and is highly invasive and often cannot be cured by surgery. Despite considerable research, treatment has not altered significantly, and the median survival remains at 9 - 12 months despite maximal safe resection, radiotherapy and chemotherapy.

Little is known about what causes brain tumours but we do know they have certain common genes that are either over-activated or mutated and these genes often encode growth factor proteins or other molecules that regulate the growth or invasion properties of the cell. Much of our research work is aimed at identifying the important genes, how they work together in pathways that lead to cancer, and where along these pathways, potential target molecules exist. Finding these effective targets has led to successful new drug therapies for breast cancer, renal cancer and leukaemia among others over the last decade, and much hope exists for the same to happen in brain tumour treatment. Additionally, we are looking into better ways to test for and monitor brain tumour treatment, as well as the mechanisms of why seizures occur.

Importantly our interdisciplinary research team has established a large brain tumour bank of archived tumour tissue and patient serum/plasma. We have also established a large library of patient-derived glioma organoids. These unique research tools are at the forefront of our collective research efforts.
Specifically, our research team is exploring several research areas concurrently, with the overarching aim of improving glioblastoma diagnosis and treatment. These areas of research include:
1. Identification and validation of serum biomarkers that can predict the presence of glioblastoma, recurrence of glioblastoma post-treatment and the efficacy of standard and novel treatments.
2. Furthering our understanding of the pro-tumorigenic properties of glioblastoma, including the molecular mechanisms used by these tumours to survive and continue to proliferate in sub-optimal environments and invade surrounding areas of the brain.
3. Pre-clinical testing of re-purposed and novel agents against several glioblastoma specific in vitro and in vivo models.

Staff

Research Group

Associate Professor Andrew Morokoff

Dr Rod Luwor, Winter and Glover Fellowship in Cancer Research

Dr Stanley Stylli, Post-Doctoral Scientist

Collaborators

The Royal Melbourne Hospital

Melbourne Private Hospital

Peter MacCallum Cancer Institute

Walter & Eliza Hall Institute

Bio21

Hadassah Institute, Israel

Imperial College London

Funding

Cure Brain Cancer Foundation

Brain Foundation Australia

NHMRC

The Royal Melbourne Hospital Neuroscience Foundation.

Research Publications

View Professor Kate Drummond's latest PubMed publications here
View Associate Professor Andrew Morokoff's latest PubMed publications here
View Dr Rod Luwor's latest PubMed publications here
View Dr Stanley Stylli's latest PubMed publications here

  1. Rodney Luwor, Andrew P. Morokoff, Stephanie Amiridis, Giovanna D’Abaco, Lucia Paradiso, Stanley S. Stylli, Hong P. T. Nguyen, Mark Tarleton, Kelly A. Young, Terence J. O’Brien, Phillip J. Robinson, Megan Chircop, Adam McCluskey & Nigel C. Jones (2019) Targeting Glioma Stem Cells by Functional Inhibition of Dynamin 2: A Novel Treatment Strategy for Glioblastoma, Cancer Investigation, DOI: 10.1080/07357907.2019.1582060
  2. Neal, A., B. A. Moffat, J. M. Stein, R. P. R. Nanga, P. Desmond, R. T. Shinohara, H. Hariharan, R. Glarin, K. Drummond, A. Morokoff, P. Kwan, R. Reddy, T. J. O'Brien and K. A. Davis (2019). "Glutamate weighted imaging contrast in gliomas with 7Tesla magnetic resonance imaging." Neuroimage Clin 22: 101694.
  3. Atkins, R. J., Stylli, S. S., Kurganovs, N., Mangiola, S., Nowell, C. J., Ware, T. M., N. M. Corcoran, D. V. Brown, A. H. Kaye, A. Morokoff, R. B. Luwor, C. M. Hovens and Mantamadiotis, T. (2019). Cell quiescence correlates with enhanced glioblastoma cell invasion and cytotoxic resistance. Experimental Cell Research, 374(2), 353-364 doi:10.1016/j.yexcr.2018.12.010
  4. Cahill V, Sinclair B, Malpas CB, McIntosh AM, Chen Z, Vivash LE, O'Shea MF, Wilson SJ, Desmond PM, Berlangieri SU, Hicks RJ, Rowe CC, Morokoff AP, King JA, Fabinyi GC, Kaye AH, Kwan P, Berkovic SF, O'Brien TJ. Metabolic patterns and seizure outcomes following anterior temporal lobectomy. Ann Neurol. 2019;85(2):241-50. Epub 2019/01/05. doi: 10.1002/ana.25405. PubMed PMID: 30609109.
  5. Nguyen, H. P. T., Morokoff, A. P., Stylli, S. S., Kaye, A. H., & Luwor, R. B. (2018). Peripheral biomarkers in glioblastoma patients—is it all just HOTAIR? Non-coding RNA Investigation, 2, 32-32. doi:10.21037/ncri.2018.05.05
  6. Whitehead, C. A., H. P. T. Nguyen, A. P. Morokoff, R. B. Luwor, L. Paradiso, A. H. Kaye, T. Mantamadiotis and S. S. Stylli (2018). Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs. Transl Oncol 11(6): 1406-1418. doi:10.1016/j.tranon.2018.08.012
  7. Vespa PM, Shrestha V, Abend N, et al. The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol. Neurobiol Dis. 2018.
  8. Tubiv MA, Lutkenhoff E, Blanco MB, et al. Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study. Neurobiol Dis. 2018.
  9. Neal A, Kwan P, O'Brien TJ, Buckland ME, Gonzales M, Morokoff A (2018) IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy. Epilepsy Behav 78: 30-36 doi:10.1016/j.yebeh.2017.10.027
  10. Ma C, Nguyen HPT, Luwor RB, Stylli SS, Gogos A, Paradiso L, Kaye AH, Morokoff AP (2018) A comprehensive meta-analysis of circulation miRNAs in glioma as potential diagnostic biomarker. PLoS One 13: e0189452 doi:10.1371/journal.pone.0189452
  11. Mao, L., Whitehead, C. A., Paradiso, L., Kaye, A. H., Morokoff, A. P., Luwor, R. B., & Stylli, S. S. (2018). Enhancement of invadopodia activity in glioma cells by sublethal doses of irradiation and temozolomide. Journal of Neurosurgery, 129(3), 598-610. doi:10.3171/2017.5.JNS17845
  12. Neal A, Kwan P, Morokoff A, O’Brien TJ. Post-operative seizure prophylaxis in gliomas. Transl Cancer Res 2017;6(Suppl 6):S1006-S1009. doi: 10.21037/tcr.2017.06.51
  13. Whitehead C, Luwor R, Morokoff A, Kaye A, Stylli S. Cancer exosomes in cerebrospinal fluid. 2017 Translational Cancer Research 6, S1352-S1370. Doi: 10.21037/tcr.2017.08.31
  14. Brown, D. V., G. Filiz, P. M. Daniel, F. Hollande, S. Dworkin, S. Amiridis, N. Kountouri, W. Ng, A. P. Morokoff and T. Mantamadiotis (2017). "Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity." PLoS One 12(2): e0172791. doi: 10.1371/journal.pone.0172791
  15. Gourlay J, Morokoff AP, Luwor RB, Zhu HJ, Kaye AH, Stylli SS. The emergent role of exosomes in glioma. J Clin Neurosci. Jan 2017; 35:13-23.
  16. Tully PA, Gogos AJ, Love C, Liew D, Drummond KJ, Morokoff AP. Reoperation for Recurrent Glioblastoma and Its Association with Survival Benefit. Neurosurgery. Nov 2016;79(5):678-689.
  17. Neal A, Morokoff A, O'Brien TJ, Kwan P. Postoperative seizure control in patients with tumor-associated epilepsy. Epilepsia. Nov 2016;57(11):1779-1788.
  18. Bennett IE, Field KM, Hovens CM, Morokoff AP et al. Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin. (2017) J Neurooncol. 131(2):321-329. doi: 10.1007/s11060-016-2300-0. Epub 2016 Nov 28.
  19. Neal A, Yuen T, Bjorksten AR, Kwan P, O'Brien TJ, Morokoff A. Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas. J Neurooncol 2016 129(2):259-67. PMID: 27311724
  20. Areeb Z, Stylli SS, Ware TM, Harris NC, Shukla L, Shayan R, Paradiso L, Li B, Morokoff AP, Kaye AH, Luwor RB. Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib. Med Oncol. 2016 May;33(5):53. doi: 10.1007/s12032-016-0767-3. Epub 2016 Apr 20. PubMed PMID: 27098175.
  21. Siegal T, Charbit H, Paldor I, Zelikovitch B, Canello T, Benis A, Wong ML, Morokoff AP, Kaye AH, Lavon I (2016) Dynamics of circulating hypoxia-mediated miRNAs and tumor response in patients with high-grade glioma treated with bevacizumab. J Neurosurg 125: 1008-1015 doi:10.3171/2015.8.JNS15437
  22. Areeb Z, Stylli SS, Koldej R, Ritchie DS, Siegal T, Morokoff AP, Kaye AH, Luwor RB (2015) MicroRNA as potential biomarkers in Glioblastoma. J Neurooncol 125: 237-248 doi:10.1007/s11060-015-1912-0
  23. Bennett, I. E., Guo, H., Kountouri, N., D'Abaco G, M., Hovens, C. M., Moffat, B. A., Desmond, P., Drummond, K., Kaye, A. H., and Morokoff, A. P. (2015). Preoperative biomarkers of tumour vascularity are elevated in patients with glioblastoma multiforme. J Clin Neurosci 22, 1802-1808.