Dr Emmy Fleuren

Dr Emmy Fleuren

Conjoint Senior Lecturer

PhD, Medical Sciences (cum laude), 2014, Radboud University (RU), Nijmegen, the Netherlands

MSc, Biomedical Sciences (bene meritum), 2008, RU, Nijmegen, the Netherlands

BSc, Biomedical Sciences, 2006, RU, Nijmegen, the Netherlands

Medicine & Health
School of Clinical Medicine

I am a Senior Scientist with a dedication to improve outcomes for young sarcoma patients, and have over 10 years of expertise in translational sarcoma research. I recently relocated from London, UK, to join Children's Cancer Institute (CCI) and the Translational Tumour Biology group (TTB; A/Prof Paul Ekert), in which I lead an independent program focusing on sarcoma biology and the development of targeted therapeutic interventions. I am also the appointed Sarcoma Expert within the Preclinical Drug Testing Core (PDTC) and ZERO Childhood Cancer Program, and hold a Conjoint Senior Lecturer Appointment at the University of New South Wales (UNSW). Personalised medicine, combination therapies, phosphoproteomics and sarcomas affecting the young are my key focus areas. I further have extensive experience in in vitro and in vivo drug testing of paediatric sarcoma models and a strong background in oncogenic signal transduction. 

 

Main research activities of my team include:

 

  • Multi-omics characterisation of paediatric sarcoma patients within the ZERO Childhood Cancer program (linking genomics, transcriptomics and methylation profiles to in vitro, in vivo, and patient drug efficacy data)

 

  • Evaluate phosphoproteomics for identification of activated drug targets not identified with ZERO's current molecular platform in paediatric sarcoma patients

 

  • Pinpoint mechanism-of-action and predictive biomarkers for drugs with molecularly unexplained extraordinary responses in paediatric sarcoma models

 

We have a range of exciting student projects available, and I very much encourage enthusiastic students to contact our lab to discuss the opportunities (efleuren@ccia.org.au). 

 

  • Journal articles | 2022
    Van Erp AEM; Hillebrandt-Roeffen MHS; Van Bree NFHN; Plüm TA; Flucke UE; Desar IME; Fleuren EDG; Van Der Graaf WTA; Versleijen-Jonkers YMH, 2022, 'Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma', Sarcoma, vol. 2022, pp. 1 - 17, http://dx.doi.org/10.1155/2022/3089424
    Journal articles | 2021
    Fleuren EDG; Terry RL; Meyran D; Omer N; Trapani JA; Haber M; Neeson PJ; Ekert PG, 2021, 'Enhancing the potential of immunotherapy in paediatric sarcomas: Breaking the immunosuppressive barrier with receptor tyrosine kinase inhibitors', Biomedicines, vol. 9, pp. 1798 - 1798, http://dx.doi.org/10.3390/biomedicines9121798
    Journal articles | 2021
    Fordham AM; Ekert PG; Fleuren EDG, 2021, 'Precision medicine and phosphoproteomics for the identification of novel targeted therapeutic avenues in sarcomas', Biochimica et Biophysica Acta - Reviews on Cancer, vol. 1876, pp. 188613, http://dx.doi.org/10.1016/j.bbcan.2021.188613
    Journal articles | 2021
    Terry RL; Meyran D; Fleuren EDG; Mayoh C; Zhu J; Omer N; Ziegler DS; Haber M; Darcy PK; Trapani JA; Neeson PJ; Ekert PG, 2021, 'Chimeric antigen receptor t cell therapy and the immunosuppressive tumor microenvironment in pediatric sarcoma', Cancers, vol. 13, pp. 4704 - 4704, http://dx.doi.org/10.3390/cancers13184704
    Journal articles | 2020
    Wong M; Mayoh C; Lau LMS; Khuong-Quang DA; Pinese M; Kumar A; Barahona P; Wilkie EE; Sullivan P; Bowen-James R; Syed M; Martincorena I; Abascal F; Sherstyuk A; Bolanos NA; Baber J; Priestley P; Dolman MEM; Fleuren EDG; Gauthier ME; Mould EVA; Gayevskiy V; Gifford AJ; Grebert-Wade D; Strong PA; Manouvrier E; Warby M; Thomas DM; Kirk J; Tucker K; O’Brien T; Alvaro F; McCowage GB; Dalla-Pozza L; Gottardo NG; Tapp H; Wood P; Khaw SL; Hansford JR; Moore AS; Norris MD; Trahair TN; Lock RB; Tyrrell V; Haber M; Marshall GM; Ziegler DS; Ekert PG; Cowley MJ, 2020, 'Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer', Nature Medicine, vol. 26, pp. 1742 - 1753, http://dx.doi.org/10.1038/s41591-020-1072-4
    Journal articles | 2020
    van Erp AEM; van Houdt L; Hillebrandt-Roeffen MHS; van Bree NFHN; Flucke UE; Mentzel T; Shipley J; Desar IME; Fleuren EDG; Versleijen-Jonkers YMH; van der Graaf WTA, 2020, 'Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo', Journal of Cancer Research and Clinical Oncology, vol. 146, pp. 1659 - 1670, http://dx.doi.org/10.1007/s00432-020-03211-z
    Journal articles | 2018
    Desar IME; Fleuren EDG; van der Graaf WTA, 2018, 'Systemic Treatment for Adults with Synovial Sarcoma', Current Treatment Options in Oncology, vol. 19, http://dx.doi.org/10.1007/s11864-018-0525-1
    Journal articles | 2018
    Holme H; Gulati A; Brough R; Fleuren EDG; Bajrami I; Campbell J; Chong IY; Costa-Cabral S; Elliott R; Fenton T; Frankum J; Jones SE; Menon M; Miller R; Pemberton HN; Postel-Vinay S; Rafiq R; Selfe JL; Von Kriegsheim A; Munoz AG; Rodriguez J; Shipley J; Van Der Graaf WTA; Williamson CT; Ryan CJ; Pettitt S; Ashworth A; Strauss SJ; Lord CJ, 2018, 'Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness', Scientific Reports, vol. 8, http://dx.doi.org/10.1038/s41598-018-29043-z
    Journal articles | 2018
    Holme H; Gulati A; Brough R; Fleuren EDG; Bajrami I; Campbell J; Chong IY; Costa-Cabral S; Elliott R; Fenton T; Frankum J; Jones SE; Menon M; Miller R; Pemberton HN; Postel-Vinay S; Rafiq R; Selfe JL; von Kriegsheim A; Munoz AG; Rodriguez J; Shipley J; van der Graaf WTA; Williamson CT; Ryan CJ; Pettitt S; Ashworth A; Strauss SJ; Lord CJ, 2018, 'Erratum to: Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness (Scientific Reports, (2018), 8, 1, (10614), 10.1038/s41598-018-29043-z)', Scientific Reports, vol. 8, http://dx.doi.org/10.1038/s41598-018-30922-8
    Journal articles | 2018
    Van Erp AEM; Versleijen-Jonkers YMH; Van Der Graaf WTA; Fleuren EDG, 2018, 'Targeted therapy-based combination treatment in rhabdomyosarcoma', Molecular Cancer Therapeutics, vol. 17, pp. 1365 - 1380, http://dx.doi.org/10.1158/1535-7163.MCT-17-1131
    Journal articles | 2017
    Brandsma I; Fleuren EDG; Williamson CT; Lord CJ, 2017, 'Directing the use of DDR kinase inhibitors in cancer treatment', Expert Opinion on Investigational Drugs, vol. 26, pp. 1341 - 1355, http://dx.doi.org/10.1080/13543784.2017.1389895
    Journal articles | 2017
    Fleuren EDG; Vlenterie M; Van Der Graaf WTA; Hillebrandt-Roeffen MHS; Blackburn J; Ma X; Chan H; Magias MC; Van Erp A; Van Houdt L; Cebeci SAS; Van De Ven A; Flucke UE; Heyer EE; Thomas DM; Lord CJ; Marini KD; Vaghjiani V; Mercer TR; Cain JE; Wu J; Versleijen-Jonkers YMH; Daly RJ, 2017, 'Phosphoproteomic profiling reveals ALK and MET as novel actionable targets across synovial sarcoma subtypes', Cancer Research, vol. 77, pp. 4279 - 4292, http://dx.doi.org/10.1158/0008-5472.CAN-16-2550
    Journal articles | 2017
    Jones SE; Fleuren EDG; Frankum J; Konde A; Williamson CT; Krastev DB; Pemberton HN; Campbell J; Gulati A; Elliott R; Menon M; Selfe JL; Brough R; Pettitt SJ; Niedzwiedz W; Van Der Graaf WTA; Shipley J; Ashworth A; Lord CJ, 2017, 'ATR Is a therapeutic target in synovial sarcoma', Cancer Research, vol. 77, pp. 7014 - 7026, http://dx.doi.org/10.1158/0008-5472.CAN-17-2056
    Journal articles | 2017
    van Erp AEM; Hillebrandt-Roeffen MHS; van Houdt L; Fleuren EDG; van der Graaf WTA; Versleijen-Jonkers YMH, 2017, 'Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with the Second-Generation ALK Inhibitor Ceritinib', Targeted Oncology, vol. 12, pp. 815 - 826, http://dx.doi.org/10.1007/s11523-017-0528-z
    Journal articles | 2016
    Fleuren EDG; Zhang L; Wu J; Daly RJ, 2016, 'The kinome 'at large' in cancer', Nature Reviews Cancer, vol. 16, pp. 83 - 98, http://dx.doi.org/10.1038/nrc.2015.18
    Journal articles | 2016
    Kager L; Whelan J; Dirksen U; Hassan B; Anninga J; Bennister L; Bovee JVMG; Brennan B; Broto JM; Brugieres L; Cleton-Jansen A-M; Copland C; Dutour A; Fagioli F; Ferrari S; Fiocco M; Fleuren E; Gaspar N; Gelderblom H; Gerrand C; Gerss J; Gonzato O; van der Graaf W; Hecker-Nolting S; Herrero-Martin D; Klco-Brosius S; Kovar H; Ladenstein R; Lancia C; LeDeley M-C; McCabe MG; Metzler M; Myklebost O; Nathrath M; Picci P; Potratz J; Redini F; Richter GHS; Reinke D; Rutkowski P; Scotlandi K; Strauss S; Thomas D; Tirado OM; Tirode F; Vassal G; Bielack SS, 2016, 'The ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24-25, 2015. Workshop Report', CLINICAL SARCOMA RESEARCH, vol. 6, http://dx.doi.org/10.1186/s13569-016-0043-5
    Journal articles | 2016
    Vlenterie M; Hillebrandt-Roeffen MHS; Schaars EWM; Flucke UE; Fleuren EDG; Navis AC; Leenders WPJ; Versleijen-Jonkers YMH; van der Graaf WTA, 2016, 'Targeting Cyclin-Dependent Kinases in Synovial Sarcoma: Palbociclib as a Potential Treatment for Synovial Sarcoma Patients', Annals of Surgical Oncology, vol. 23, pp. 2745 - 2752, http://dx.doi.org/10.1245/s10434-016-5341-x
    Journal articles | 2014
    Fleuren EDG; Hillebrandt-Roeffen MHS; Flucke UE; te Loo DMWM; Boerman OC; van der Graaf WTA; Versleijen-Jonkers YMH, 2014, 'The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma', Oncotarget, vol. 5, pp. 12753 - 12768, http://dx.doi.org/10.18632/oncotarget.2648
    Journal articles | 2014
    Fleuren EDG; Versleijen-Jonkers YMH; Boerman OC; van der Graaf WTA, 2014, 'Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: Current hurdles and future perspectives', Biochimica et Biophysica Acta - Reviews on Cancer, vol. 1845, pp. 266 - 276, http://dx.doi.org/10.1016/j.bbcan.2014.02.005
    Journal articles | 2014
    Fleuren EDG; Versleijen-Jonkers YMH; Heskamp S; van Herpen CML; Oyen WJG; van der Graaf WTA; Boerman OC, 2014, 'Theranostic applications of antibodies in oncology', Molecular Oncology, vol. 8, pp. 799 - 812, http://dx.doi.org/10.1016/j.molonc.2014.03.010
    Journal articles | 2014
    Fleuren EDG; Versleijen-Jonkers YMH; Roeffen MHS; Franssen GM; Flucke UE; Houghton PJ; Oyen WJG; Boerman OC; Van Der Graaf WTA, 2014, 'Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models', International Journal of Cancer, vol. 135, pp. 2770 - 2782, http://dx.doi.org/10.1002/ijc.28933
    Journal articles | 2014
    Fleuren EDG; van der Graaf WTA; Roeffen MHS; Flucke UE; Schreuder B; Boerman O; Versleijen-Jonkers YMH, 2014, 'The Role of Axl in Ewing Sarcoma', Annals of Oncology, vol. 25, pp. iv508 - iv508, http://dx.doi.org/10.1093/annonc/mdu354.45
    Journal articles | 2013
    Fleuren EDG; Roeffen MHS; Leenders WP; Flucke UE; Vlenterie M; Schreuder HW; Boerman OC; Van Der Graaf WTA; Versleijen-Jonkers YMH, 2013, 'Expression and clinical relevance of MET and ALK in Ewing sarcomas', International Journal of Cancer, vol. 133, pp. 427 - 436, http://dx.doi.org/10.1002/ijc.28047
    Journal articles | 2013
    Fleuren EDG; Versleijen-Jonkers YMH; Heskamp S; Roeffen MHS; Bouwman WH; Molkenboer-Kuenen JDM; Van Laarhoven HWM; Oyen WJG; Boerman OC; Van Der Graaf WTA, 2013, 'The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab′)2-R1507 fragments in Ewing sarcomas', European Journal of Cancer, vol. 49, pp. 2851 - 2858, http://dx.doi.org/10.1016/j.ejca.2013.04.009
    Journal articles | 2011
    Fleuren EDG; Versleijen-Jonkers YMH; Van De Luijtgaarden ACM; Molkenboer-Kuenen JDM; Heskamp S; Roeffen MHS; Van Laarhoven HWM; Houghton PJ; Oyen WJG; Boerman OC; Van Der Graaf WTA, 2011, 'Predicting IGF-1R therapy response in bone sarcomas: Immuno-SPECT imaging with radiolabeled R1507', Clinical Cancer Research, vol. 17, pp. 7693 - 7703, http://dx.doi.org/10.1158/1078-0432.CCR-11-1488
    Journal articles | 2010
    Fleuren E; O'Toole S; Millar E; Mcneil CM; Lopez-Knowles E; Boulghourjian A; Croucher DR; Schramek D; Brummer T; Penninger JM; Sutherland RL; Daly RJ, 2010, 'Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development', International Journal of Cancer, vol. 127, pp. 1486 - 1492, http://dx.doi.org/10.1002/ijc.25172
    Journal articles | 2009
    Brummer T; Larance M; Abreu MTH; Lyons RJ; Timpson P; Emmerich CH; Fleuren EDG; Lehrbach GM; Schramek D; Guilhaus M; James DE; Daly RJ, 2009, 'The docking protein and proto-oncogene product Gab2 is regulated via a novel negative feedback mechanism mediated by 14-3-3 binding.', Cell communication and signaling : CCS, vol. 7, pp. A12 - A12, http://dx.doi.org/10.1186/1478-811X-7-S1-A12
    Journal articles | 2008
    Brummer T; Larance MC; Abreu M; Lyons RJ; Timpson P; Emmerich C; Fleuren E; Lehrbach GM; Schramek D; Guilhaus M; James DE; Daly RJ, 2008, 'Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein', European Molecular Biology Organization, vol. 27, pp. 2305 - 2316, http://dx.doi.org/10.1038/emboj.2008.159
  • Conference Papers | 2018
    Fleuren EDG; Jones S; Frankum J; Williamson C; Menon M; Shipley J; Ashworth A; Graaf WVD; Lord CJ, 2018, 'Abstract 2975: Synthetic lethality in synovial sarcoma: SS18-SSX fusions and DNA damage response (DDR) inhibitors', in Cancer Research, American Association for Cancer Research (AACR), pp. 2975 - 2975, presented at Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL, http://dx.doi.org/10.1158/1538-7445.am2018-2975
    Conference Papers | 2017
    Fleuren ED; Vlenterie M; van der Graaf W; Hillebrandt-Roeffen M; Cebeci S; van de Ven A; Flucke U; Wu J; Versleijen-Jonkers Y; Daly R, 2017, 'Phosphoproteomic landscape of sarcoma: novel subgroups and actionable targets', in CANCER RESEARCH, AMER ASSOC CANCER RESEARCH, DC, Washington, presented at Annual Meeting of the American-Association-for-Cancer-Research (AACR), DC, Washington, 01 April 2017 - 05 April 2017, http://dx.doi.org/10.1158/1538-7445.AM2017-5837
    Conference Papers | 2013
    Fleuren EDG; Versleijen-Jonkers YMH; Roeffen MHS; Franssen GM; Houghton PJ; Oyen WJG; Boerman OC; van der Graaf WTA, 2013, 'Abstract 2761: Temsirolimus is effective as a single agent and in combination with cisplatin or bevacizumab in preclinical osteosarcoma models.', in Cancer Research, American Association for Cancer Research (AACR), pp. 2761 - 2761, presented at Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC, http://dx.doi.org/10.1158/1538-7445.am2013-2761
    Conference Papers | 2011
    Fleuren EDG; Versleijen-Jonkers YMH; van de Luijtgaarden ACM; Molkenboer-Kuenen JDM; Roeffen MHS; van Laarhoven HWM; Boerman OC; Oyen WJG; van der Graaf WTA, 2011, 'Abstract 5283: MicroSPECT imaging of IGF1R expression with radiolabeled R1507 in osteosarcoma models', in Cancer Research, American Association for Cancer Research (AACR), pp. 5283 - 5283, presented at Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL, http://dx.doi.org/10.1158/1538-7445.am2011-5283

 



 

  • 2020, AI, Research Grant - ANZSA Xavier K Foundation
  • 2020, CIB, Pioneering Research Grant – Tour de Cure
  • 2020, CI, Two-year project grant: Emerging Research Leader Program – CanToo
  • 2016, CITwo-year Rubicon Fellowship - Netherlands Organisation for Scientific Research (NWO) 
  • 2014, CIA, Research grant - Stichting HDKT

CI = (sole) Chief Investigator; CIA/B = Chief Investigator A/B; AI = Associate Investigator

2019:   Early Career Researcher Travel Grant – Kids Cancer Alliance (KCA)

2019:   Early Career Researcher (ECR) Rapid-fire 2nd place - KCA

2018:   Travel grant – Biochemical Society

2017:   Young Researcher Award - EURO EWING Consortium (EEC) and Peter Pan Charity

2016:   Featured article in Nat Rev Cancer (Fleuren 2016; Nat Rev Cancer;16:83–98) 

2015:   Best Oncology thesis of the Netherlands and Vlaanderen 2015 – NVMO

2014:   Travel grant - Dutch Cancer Society (KWF) 

2011:   Article and image in highlights section Clin Cancer Research (Clin Cancer Res 2011;17:7503)

Publications:

• van Erp AEM, …, Fleuren EDG, Versleijen-Jonkers Y, van der Graaf WTA. Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo. J Cancer Res Clin Oncol 2020; 146:1659-1670.

• Holme H‡, Gulati A‡, Brough R‡, Fleuren EDG, et al. Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. Sci Rep 2018;8(1):10614.

• van Erp AEM, Versleijen-Jonkers YMH, van der Graaf WTA, Fleuren EDG. Targeted therapy-based combination treatment rhabdomyosarcoma. Mol Cancer Ther 2018:17;1365-1380.

• Desar I, Fleuren E, et al. Systemic treatment for adults with synovial sarcoma. Curr Treat Options Oncol 2018:19;13.

• van Erp AEM, Hillebrandt-Roeffen MHS, van Houdt L, Fleuren EDG, et al. Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with second-generation ALK inhibitor Ceritinib. Target Oncol 2017;12:815-826.

• Jones SE‡, Fleuren EDG‡, et al. ATR is a therapeutic target in synovial sarcoma. Cancer Res 2017;77:7014-7026.

• Brandsma I, Fleuren EDG, et al. Directing the use of DDR inhibitors in cancer treatment. Expert Opin Investig Drugs 2017;26:1341-1355.

Fleuren EDG‡, Vlenterie M‡, et al. Phosphoproteomic profiling reveals ALK and MET as novel actionable targets across synovial sarcoma subtypes. Cancer Res 2017;77:4279-4292.

• Vlenterie M, Hillebrandt-Roeffen MH, Schaars EW, Flucke UE, Fleuren ED, et al. Targeting the cyclin D1 pathway in Synovial Sarcoma. Ann Surg Oncol 2016; 23:2745–2752.

Fleuren ED‡, Zhang L‡, Wu J, Daly RJ. The kinome ‘at large’ in cancer. Nat Rev Cancer 2016;16:83–98.

Fleuren ED et al. The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma. Oncotarget 2014;5:12753-68.

Fleuren ED et al. Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models. Int J Cancer 2014;135:2770-82.

Fleuren ED, et al. Theranostic applications of antibodies in oncology. Mol Oncol 2014;8:799-812.

Fleuren ED et al. Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: current hurdles and future perspectives. Biochim Biophys Acta - Reviews on Cancer 2014;1845:266-76.

Fleuren ED et al. The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab’)2-R1507 fragments in Ewing sarcomas. Eur J Cancer 2013;49:2851-2858.

Fleuren ED et al. Expression and clinical relevance of MET and ALK in Ewing sarcomas. Int J Cancer 2013;133:427-436.

Fleuren ED et al. Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507. Clin Cancer Res 2011;17:7693-703.

Fleuren ED et al. Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development. Int J Cancer 2010;127:1486-92.

• Brummer T, Larance M, Herrera Abreu MT, Lyons RJ, Timpson P, Emmerich CH, Fleuren ED, et al. Phosphorylationdependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. EMBO J 2008 3;27:2305-16.