Research
Our lab works on the clinical and molecular aspects of solid tumours of childhood, particularly germ cell tumours (GCTs) – of which testicular cancer is the most common form. Our work has established emphasis on the role of non-coding RNAs such as microRNAs, which are short, non-protein-coding RNAs that regulate gene expression post-transcriptionally and are aberrantly expressed in cancer. We demonstrated for the first time that the miR-371~373 and miR-302/367 clusters are highly over-expressed in all malignant GCTs, regardless of patient age, histological subtype or anatomical site (published in Cancer Research in 2010). This is a specific change, as these microRNAs are not co-ordinately dysregulated in any other malignancy or disease state. We subsequently were the first to demonstrate the potential utility of specific circulating microRNAs for diagnosis, disease-monitoring and detection of relapse in GCTs as well as other childhood tumours.
Our current research has four main overarching themes:
1) Exploring clonal dynamics of germ cell tumours
We are undertaking comprehensive molecular profiling of germ cell tumours, to uncover their spatio-temporal relationship and phylogeny. This work will facilitate our understanding of the mechanisms of cisplatin sensitivity and resistance.
2) Role of the tumour microenvironment in testicular germ cell tumours
This work includes an exploration of the role of tumour-derived extracellular vesicles and their cargo on cells of the tumour microenvironment.
3) Novel therapeutic approaches in malignant germ cell tumours
Having investigated the effects of restoring levels of under-expressed microRNAs in malignant GCTs, highlighting the importance of the LIN28/let-7 axis (published in Cancer Research), we are now exploring the potential of replenishing other putative tumour-suppressor microRNAs, as well as investigating the consequences of targeting over-expressed microRNAs.
4) Improving diagnostic and disease-monitoring approaches for cancer, including germ cell tumours
Following demonstration that levels of microRNAs from the miR-371~373 and miR-302/367 clusters are elevated in the serum at malignant GCT diagnosis, may be tracked during treatment and are sensitive for relapse detection (published in American Journal of Clinical Pathology, Nature Reviews Urology and British Journal of Cancer), we now have serum microRNA outcomes embedded in prospective international clinical trials and are developing the assay for clinical use. We are also identifying serum microRNAs that can be used for risk-stratification and prognosis. We have also highlighted the potential clinical utility of circulating microRNA profiles in other solid tumours of childhood, including high-risk MYCN-amplified neuroblastoma.
Publications
(since 2015)
- Murray MJ, Ajithkumar TV, Harris F, Williams RM, Jalloh I, Cross J, Ronghe M, Ward D, Scarpini CG, Nicholson JC and Nicholas Coleman, on behalf of the CCLG. Clinical utility of circulating miR-371a-3p for the management of patients with intracranial malignant germ cell tumors. Neuro-Oncology Advances, In Press, 2020
- Hayden J*, Murray MJ*, Bartels U, Penn A, Calaminus G, Nicholson JC. Symptom interval and treatment burden for intracranial malignant germ-cell-tumour patients. Archives of Disease in Childhood, 2020 Mar;105(3):247-252. *Joint first authors.
- Murray MJ, Ruffle A, Lowis S, Howell L, Whitton S, Dommett R, Gamble A, Shenton G, Nicholson JC. A Delphi method to identify expert opinion to support NICE children’s cancer referral guidelines. Archives of Disease in Childhood, 2020 Mar;105(3):241-246.
- Lafin JT, Singla N, Woldu S, Lotan Y, Lewis CM, Majmudar K, Zhou M, Kapur P, Margulis V, Murray MJ, Amatruda JF, Bagrodia A. Serum microRNA-371a-3p levels predict viable germ cell tumor in chemotherapy-naïve patients undergoing retroperitoneal lymph node dissection. European Urology, 2020 Feb;77(2):290-292.
- Murray MJ, Coleman N. Can circulating microRNAs quantification solve clinical dilemmas in testicular germ cell malignancy? Nature Reviews Urology, Sep;16(9):505-506.
- Frazer JL, Hook CE, Addley HC, Jackson CR, Latimer J, Nicholson JC, Murray MJ. Recurrent ovarian immature teratoma in a 12-year-old girl: implications for management. Gynecologic Oncology, 2019;154:259-265.
- Charytonowicz D, Aubrey H, Bell C, Ferret M, Tsui K, Atfield R, Coleman N*, Murray MJ*, Wilson E*. A cost analysis of non-invasive blood-based microRNA testing versus CT scans for follow-up in patients with testicular germ cell tumors. Clinical Genitourinary Cancer, 2019;17:e733-e744. *joint senior authors.
- Murray MJ, Coleman N. Understanding the pathway - MicroRNA dysregulation in malignant germ cell tumors: more than a biomarker? Journal of Clinical Oncology, 2019;37:1432-1435.
- Frazier LA, Stoneham S, Rodriguez-Galindo C, Dang H, Xia C, Olson TA, Murray MJ, Amatruda J, Arul SG, Shaikh F, Billmire D, Krailo MD, Stark D, Brougham MF, Nicholson JC, Hale JPH. Comparison of Carboplatin vs. Cisplatin in the Treatment of Paediatric Malignant Germ Cell Tumours: A Report of the Malignant Germ Cell International Consortium. European Journal of Cancer, 2018;98:30-37.
- Murray MJC*, Watson HL*, Ward D, Bailey S, Ferraresso M, Nicholson JC, Gnanapragasam VJ, Thomas B, Scarpini CG, Coleman N. ‘Future-proofing’ blood processing for measurement of circulating microRNAs in samples from biobanks and prospective clinical trials. Cancer Epidemiology, Biomarkers and Prevention, 2018;27:208-218 *joint first authors.
- Murray MJ, Turnbull C. Testicular Cancer in 2017 – Sequencing advances understanding. Nature Reviews Urology, 2018;15:79-80.
- Calaminus G, Frappaz D, Kortmann RD, Krefeld B, Saran F, Pietsch T, Vasiljevic A, Garre ML, Ricardi U, Mann JR, Goebel U, Alapetite C, Murray MJ, Nicholson JC. Outcome of patients with intracranial non-germinomatous germ cell tumors - lessons from the SIOP-CNS-GCT-96 trial. Neuro-Oncology, 2017;19:1661-1672.
- Murray MJ, Bailey S, Heinemann K, Mann J, Göbel UK, Saran S, Hale JP, Calaminus C, Nicholson JC. Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy, International Journal of Cancer, 2017;141:621-635.
- Murray MJ, Huddart RA, Coleman N. The present and future of serum diagnostic tests for testicular malignant germ cell tumours. Nature Reviews Urology, 2016;13:715-725.
- Shaikh F, Murray MJ, Amatruda JF, Coleman N, Nicholson JC, Hale JPH, Pashankar F, Stoneham SJ, Poynter JN, Olson TA, Billmire DF, Stark D, Rodriguez-Galindo C, Frazier AL. Paediatric extracranial germ cell tumours. Lancet Oncology, 2016;17:e149-62.
- Murray MJ*, Bell E*, Raby K, Rijlaarsdam M, Gillis A, Looijenga LH, et al. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ cell tumours. British Journal of Cancer, 2016;114:151-62. *joint first authors.
- Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC. Consensus in the management of intracranial germ-cell tumours. Lancet Oncology, 2015;16:e470-7.
- Olson TA, Murray MJ, Rodriguez-Galindo C, Nicholson JC, Billmire DF, Krailo MD, et al. Pediatric and Adolescent Extracranial Germ Cell Tumors - The Road to Collaboration. Journal of Clinical Oncology, 2015;33:3018-3028.
- Frazier AL, Hale JP, Rodriguez-Galindo C, Dang H, Olson T, Murray MJ, et al. Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data from the United Kingdom and United States. Journal of Clinical Oncology, 2015;33:195-201.
- Murray MJ, Raby KL, Saini HK, Bailey S, Wool SV, Tunnacliffe JM, Enright AJ, Nicholson JC, Coleman N. Solid tumors of childhood display specific serum microRNA profiles. Cancer Epidemiology, Biomarkers & Prevention, 2015;24:350-60.
