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Towards personalised medicine for cancerFrom initial therapy to follow-upMolenaar, R.J.

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Citation for published version (APA):Molenaar, R. J. (2017). Towards personalised medicine for cancer: From initial therapy to follow-up.

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246

Appendix: PhD portfolio

PhD student: Remco J. Molenaar PhD period: August 2013 - July 2017 PhD supervisors:

• Professor Cornelis J.F. van Noorden, PhD (promotor) • Professor W. Peter Vandertop, MD PhD (promotor) • Johanna W. Wilmink, MD PhD (co-promotor) • Fonnet E. Bleeker, MD PhD (co-promotor)

1. PhD training Description Year ECTS General courses • Practical Biostatistics • Clinical Data Management • BROK (‘Basiscursus Regelgeving Klinisch Onderzoek’)

2014 2014 2015

1.1 0.9 1.0

Seminars, workshops and master classes • Cancer Center Amsterdam Meet-the-Expert session: o Tamara Lah (National Institute of Biology, Ljubljana) o Colin Watts (University of Cambridge) o Arie Perry (University of California, San Francisco) o David Louis (Massachusetts General Hospital, Boston) o David Ellison (St. Jude’s Children Research Hospital, Memphis) o Roel Verhaak (MD Anderson, Houston)

• Spinoza professor Master Class by Daphne Haas-Kogan (Dana-Farber Cancer Institute, Boston)

2012 2013 2014 2015 2015 2016 2015

0.2 0.2 0.2 0.2 0.2 0.2 0.4

Presentations • “IDH1/2-Mutated Acute Myeloid Leukemia Has Impaired DNA Damage Response

and Is Sensitive to Monotherapy with the PARP Inhibitior Olaparib” Oral presentation at the American Society of Hematology (ASH) 2017 Annual Meeting, 3-7 December 2017, Atlanta, GA, United States.

2017 0.5

• “High Rates of Atherosclerotic Disease-Related Mortality in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia Patients Associated with TET2 Mutations” Oral presentation at the American Society of Hematology (ASH) 2017 Annual Meeting, 3-7 December 2017, Atlanta, GA, United States.

2017 0.5

• “Risk of developing acute myeloid leukemia in well-differentiated thyroid cancer patients treated with radioactive iodine: a population-based study” Oral presentation at the European Society of Medical Oncology 2017 Congress, ESMO Congress 2017, 8-12 September, Madrid, Spain.

2017 0.5

• “The effect of research on IDH1 mutations on stock prices” OASIS Lecture. 2015 0.2 • “Radioprotection of IDH1-mutated cancer cells by and IDH1-mutated inhibitor”

Science Night of the Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands.

2015 0.2

• “IDH1 mutations in acute myeloid leukaemia: friend or foe?” Seminar at the Department of Translational Haematology & Oncology Research at the Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

2015 0.2

• Workshops on Academic Writing & Presenting, MVM Mozaiek, Amsterdam Medical Student journal, Honours Programme Medicine and CoRaad.

2015-2017 2.0

• “IDH1 mutations in glioblastoma decrease NADPH production capacity and sensitise for irradiation” Oral presentation at the Dutch Cancer Society, Annual Meeting on tumour cell biology

2014 0.5

• “An inhibitor of IDH1R132H, protects IDH1R132H cells against irradiation” Oral presentation at the European Association for Neuro-Oncology

2014 0.5

• “IDH1 als onafhankelijke prognostische factor in glioblastoma” Oral presentation at the Dutch Society for Neuro-Oncology

2011 0.5

• Poster presentations at various conferences

2013-2017 4.0

Appendix: PhD portfolio

247

(Inter)national conferences • Dutch Society for Neuro-Oncology, Annual Meeting, Maastricht, The

Netherlands. 2011 0.4

• New England Journal of Medicine, 200th anniversary meeting, Boston, Massachusetts, United States.

2012 0.4

• Dutch Society for Neuro-Oncology, Annual Meeting, Utrecht, The Netherlands. 2013 0.4 • Dutch Cancer Society, Annual Meeting on tumour cell biology, Lunteren, The

Netherlands. 2013 0.6

• Oncology Graduate School of Amsterdam, annual Ph.D. student retreat, Renesse, The Netherlands

2013 0.8

• Lindau Nobel Laureate Meeting in Physiology and Medicine, Lindau, Germany. 2014 1.5 • Czech Histochemical Society, Annual Meeting, Brno, Czech Republic 2014 1.0 • Dutch Society for Neuro-Oncology, Annual Meeting, Utrecht, The Netherlands. 2014 0.4 • Society for Neuro-Oncology (SNO), Annual Meeting, Miami, FL, United States. 2014 1.0 • Keystone Symposium on Integrating Metabolism and Tumour Biology,

Vancouver, Canada. 2015 1.0

• American Association for Cancer Research (AACR), New Horizons in Cancer Research, Shanghai, China.

2015 1.0

• American Society of Haematology (ASH), Annual Meeting, Orlando, FL, United States.

2015 1.0

• American Association for Cancer Research (AACR) Annual Meeting, New Orleans, LA, United States.

2016 1.0

• Dutch Society for Neuro-Oncology, Annual Meeting, Utrecht, The Netherlands. 2016 0.4 • American Society of Haematology (ASH), Annual Meeting, San Diego, CA, United

States. 2016 1.0

• MDS Foundation International Symposium on Myelodysplastic Syndromes, Valencia, Spain.

2017 1.0

• American Society of Clinical Oncology (ASCO), Annual Meeting, Chicago, IL, United States.

2017 1.0

• European Society of Medican Oncology (ESMO), Annual Meeting, Madrid, Spain.

2017 1.0

Other • Organizing Board, APROVE Annual Scientific Meeting 2014 3.0 • Editorial Board (Oncology Section), Amsterdam Medical Student Journal 2016-now 0.5 • Editorial Board, Journal of Clinical and Translational Research 2015-now 0.2 • Secretary of the Board, Dutch Society for Neuro Oncology - Investigators 2013-now 4.0 • Weekly department seminars 2012-2015 3.0 • OASIS seminars 2012-2015 3.0

2. Teaching Description Year ECTS Course coordinator • Brain Tumors (Bachelor’s level course, Medicine, University of Amsterdam, The

Netherlands).

2015-2017 4.0

Lecturer • Clinical Cell Biology (Master’s level course, Biomedical Sciences, University of

Amsterdam, The Netherlands). 2012-present 1.0

• Brain Tumors (Bachelor’s level course, Medicine, University of Amsterdam, The

Netherlands). 2013-2017 4.0

• Human Body II (Bachelor’s level course, Amsterdam University College, The Netherlands).

2014-2017 3.0

• Cellular Oncology (Bachelor’s level course, Biomedical Sciences, University of Amsterdam, The Netherlands).

2014-2017 3.0

Tutoring, Mentoring • M. Haenen, Master’s level literature thesis, Biomedical Sciences 2013 0.5 • D. Dimitrakopoulou, Master’s level laboratory internship, Biomedical Sciences. 2013-2014 2.0 • A.R. Luning, Bachelor’s level thesis and laboratory internship, Amsterdam

University College, Major: Life Sciences. 2014 0.5

• Y. Nushi, Bachelor’s level thesis, Medicine. 2014 0.5 • M. Dutilh, Bachelor’s level thesis, Medicine. 2014 0.5

Appendix: PhD portfolio

248

• M.P. Witvliet, Bachelor’s level thesis, Medicine. 2014-2015 0.5 • V.V.V. Hira, Master’s level laboratory internship, Biomedical Sciences. 2014-2015 2.0 • R. Hulsbos, Bachelor’s level laboratory internship, Biomedical Sciences. 2014-2015 1.0 • V.V.V. Hira, Master’s level thesis, Biomedical Sciences. 2015 1.0 • D. Botman, Master’s level thesis, Biomedical Sciences. 2015 1.0 • N. Aarnoudse, Bachelor’s level thesis and laboratory internship, Amsterdam

University College. 2015-2016 1.0

• F. Maidman, Bachelor’s level thesis, Medicine. 2015-2016 0.5 • J.R. Wormer, Bachelor’s level thesis, Medicine. 2015-2016 0.5 • A.J.G. Meeuwisse, Bachelor’s level thesis, Medicine. 2015-2016 0.5 • T. van de Venne, Master’s level internship and thesis, Medicine. 2016 2.0 • Q.S. van Keulen, Bachelor’s level thesis, Medicine. 2016-2017 0.5 • K.S. van der Lee, Master’s level internship and thesis, Medicine. 2017 2.0 • B.C Bosman, Bachelor’s level research fellowship, Medicine. 2017 0.5 • H.A.J. Eversdijk, Bachelor’s level research fellowship, Medicine. 2017 0.5 • J.B.M.C. van Megen, Bachelor’s level thesis, Medicine. 2017 0.5

3. Parameters of esteem Description Year Grants • AMC PhD Scholarship (€220,000) 2013 • Dutch Cancer Society (KWF) grant (UVA2014-6839), van Noorden CJ, Leenders WP, Span PN:

IDH mutations as template for novel therapies in cancer, €567,200 – writing committee 2014

• Dutch Cancer Society (KWF) grant (10460), Wilmink JW, van Noorden CJ, Bovee JVMG: Something old, something new: Repurposing already-approved metabolic drugs to target IDH1/2 mutations in cancer, €181,137 – writing committee

2016

Awards and honours • Silver Scholar winner in essay contest of the New England Journal of Medicine, Boston, MA, United

States. 2012

• Young scientist award of the Dutch Royal Academy of Sciences (KNAW) to attend the Lindau Nobel Laureate Conference 29 June – 4 July 2014 in Lindau, Germany.

2014

• American Association for Cancer Research (AACR) Scholar-in-Training Award – New Horizons in Cancer Research Conference, 11-15 November 2015, Shanghai, China.

2015

• American Society of Hematology (ASH) Abstract Achievement Award – ASH Annual Meeting 2015, 5-9 December 2015, Orlando, FL, United States.

2015

• American Association for Cancer Research (AACR) and Warner Fund Scholar-in-Training Award – AACR Annual Meeting 2016, 16-20 April 2016, New Orleans, LA, United States.

2016

• Academic Medical Center Graduate School of Medicine PhD awards 2016, Best Poster Prestented by a PhD student – nominee.

2016

• Academic Medical Center Graduate School of Medicine PhD awards 2016, Best Paper Published by a PhD student - 2nd prize;

2016

• American Society of Hematology (ASH) Abstract Achievement Award – ASH Annual Meeting 2016, 2-6 December 2016, San Diego, CA, United States.

2016

• European Society of Medical Oncology (ESMO) Travel Grant – ESMO Congress 2017, 8-12 September, Madrid, Spain.

2017

• Selected for “ESMO 2017 Highlights in Haematological Malignancies” at ESMO Congress 2017, 8-12 September, Madrid, Spain.

2017

• American Society of Hematology (ASH) Abstract Achievement Award – ASH Annual Meeting 2017, 3-7 December 2017, Atlanta, GA, United States.

2017

• Selected for “2018 Highlights of ASH in Myelodysplastic Syndromes”, San Francisco, CA and Washington, DC, 12-13 January 2018; Dallas, TX and Miami, FL, 19-20 January 2018; Chicago, IL and New York, NY, 26-27 January 2018, all in the United States; Bali, Indonesia, 9-10 March 2018 and Rio de Janeiro, Brazil, April 27-28 2018.

2017

4. Publications Publications: 29 Citations: 538 Hirsch index: 12 Publications in peer-reviewed journals First or last authorship:

1. Molenaar RJ. Ion channels in glioblastoma. ISRN Neurology. 2011; 590249.674

Appendix: PhD portfolio

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2. Molenaar RJ, Verbaan D, Lamba S, Zanon C, Jeuken JW, Boots-Sprenger SH, Wesseling P, Hulsebos TJ, Troost D, van Tilborg AA, Leenstra S, Vandertop WP, Bardelli A, van Noorden CJ, Bleeker FE. The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. Neuro Oncology. 2014; 16:1263-73.289

3. Molenaar RJ, Radivoyevitch T, Maciejewski JP, van Noorden CJ, Bleeker FE. The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation. Biochim Biophys Acta Reviews on Cancer. 2014; 1846:326-41.15

4. Molenaar RJ, van Noorden CJ. Type 2 diabetes and cancer as redox diseases? The Lancet. 2014; 384:853.1

5. Molenaar RJ, Thota S, Nagata Y, Patel B, Clemente M, Hirsh C, Viny AD, Hosano N, Bleeker FE, Meggendorfer M, Alpermann T, Shiraishi Y, Chiba K, Tanaka H, van Noorden CJ, Radivoyevitch T, Carraway HE, Makishima H, Miyano S, Sekeres MA, Ogawa S, Haferlach T, Maciejewski JP. Clinical and biological implications of ancestral and non-ancestral IDH1 and IDH2 mutations in myeloid neoplasms. Leukemia. 2015; 29:2134-42.280

6. Molenaar RJ, Botman D, Smits MAJ, Hira VVV, van Lith SAM, Navis AC, Dimitrakopoulou D, van Drunen CM, Radivoyevitch T, Leenders WPJ, Stap J, Vandertop WP, Bleeker FE, van Noorden CJF. The IDH1-mutant inhibitor AGI-5198 protects IDH1-mutated cancer cells against irradiation. Cancer Research. 2015; 75:4790-802.143

7. Molenaar RJ, Coelen JS, Khurshed M, Roos E, Caan MWA, van Linde ME, Kouwenhoven M, Bramer JAM, Bovee JVMG, Mathot RAA, Klümpen HJ, van Laarhoven HWM, van Noorden CJF, Vandertop WP, Gelderblom AJ, van Gulik TM, Wilmink JW. Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours. British Medical Journal Open. 2017; 7:e014961.256

8. Hira VVV, van Noorden CJF, Carraway HE, Maciejewski JP, Molenaar RJ. Novel therapeutic strategies to target leukaemic cells that hijack haematopoietic stem cell niches. Biochim Biophys Acta Reviews on Cancer. 2017; 1868:183-98.497

9. Molenaar RJ, Radivoyevitch T, Wilmink JW. Re: Colorectal Cancer Incidence Patterns in the United States, 1974-2013. Journal of the National Cancer Insitute. 2017; 109:djx103.675

10. Molenaar RJ, van de Venne T, Weterman MA, Mathot RAA, Klümpen HJ, Richel D, Wilmink JW. A phase Ib/II study of everolimus combined with metformin for patients with advanced cancer. Invest New Drugs. 2017; doi: 10.1007/s10637-017-0478-4.257

11. Molenaar RJ, Wilmink JW. Cancer incidence in the aging population. Amsterdam Medical Student Journal. 2017; 8:35-6.

12. Molenaar RJ, Khurshed M, Hira VV, van Noorden CJF. Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues. Journal of Visualized Experiments. 2017; e56843.

13. Molenaar RJ, Pleyer C, Radivoyevitch T, Sidana S, Godley A, Advani AS, Gerds AT, Carraway HE, Kalaycio M, Nazha A, Adelstein DJ, Nasr C, Angelini D, Maciejewski JP, Majhail NS, Sekeres MA, Mukherjee S. Risk of developing chronic myeloid neoplasms in well-differentiated thyroid cancer patients treated with radioactive iodine: a population study. Leukemia. 2017; doi: 10.1038/leu.2017.323.596

14. Molenaar RJ, Sidana S, Radivoyevitch T, Advani AS, Gerds AT, Carraway HE, Angelini D, Kalaycio M, Nazha A, Adelstein DJ, Nasr C, Maciejewski JP, Majhail NS, Sekeres MA, Mukherjee S. Risk of haematologic malignancies following radioiodine treatment for well-differentiated thyroid cancer. Journal of Clinical Oncology. 2017; in press.

15. Molenaar RJ, Maciejewski JP, Wilmink JW, van Noorden CJ. Wild-type and mutated IDH1/2 enzymes and therapy responses. Oncogene. 2017; in press.

16. Molenaar RJ, Radivoyevitch T, Nagata Y, Khurshed M, Pryzchodzen B, Makishima H, Xu M, Bleeker FE, Wilmink JW, Carraway HE, Mukherjee S, Sekeres MA, van Noorden CJ, Maciejewski JP. IDH1/2 mutations sensitize acute myeloid leukemia to PARP inhibition this is reversed by IDH1/2-mutant inhibitors. Clinical Cancer Research. 2017; in press.

Co-authorship:

17. Amin AS, Boink GJ, Atrafi F, Spanjaart AM, Asghari-Roodsari A, Molenaar RJ, Ruijter JM, Wilde AA, Tan HL. Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome. Europace. 2012; 13:968-75.676

18. Bleeker FE, Molenaar RJ, Leenstra S. Recent advances in the molecular understanding of glioblastoma. Journal of Neurooncology. 2012; 108:11-27.54

19. van Lith SA, Navis AC, Verrijp K, Niclou SP, Bjerkvig R, Wesseling P, Tops B, Molenaar RJ, van Noorden CJ, Leenders WP. Glutamate as chemotactic fuel for diffuse glioma cells: Are they glutamate suckers? Biochim Biophys Acta Reviews on Cancer. 2014; 1846:66-74.16

20. van Lith SA, Molenaar RJ, van Noorden CJ, Leenders WP. Tumour cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas. Neuro Oncology. 2014; 16:1669-70.244

Appendix: PhD portfolio

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21. Bleeker FE, Lamba S, Zanon C, Molenaar RJ, Hulsebos TJ, Troost D, van Tilborg AA, Vandertop WP, Leenstra S, van Noorden CJ, Bardelli A. Mutational profiling of kinases in glioblastoma. BioMed Central Cancer. 2014; 14:718.395

22. Hira VVV, Ploegmakers K, Grevers F, Verbovsek U, Silvestre-Roig C, Aronica E, Tigchelaar W, Turnsek TL, Molenaar RJ, van Noorden CJF. CD31+, CD133+ and nestin+ perivascular glioma stem-like cell niches express SDF-1α, CXCR4, osteopontin and cathepsin K. Journal of Histochemistry and Cytochemistry. 2015; 63:481-93.677

23. Radivoyevitch T, Sachs RK, Gale RP, Molenaar RJ, Brenner DJ, Kalaycio ME, Carraway HE, Mukherjee S, Sekeres MA, Maciejewski JP. Defining AML and MDS second cancer risk dynamics after diagnosis of first cancers treated or not with radiation. Leukemia. 2016; 30:285-94.489

24. Nijland PG, Molenaar RJ, van der Pol SMA, van der Valk P, van Noorden CJF, De Vries HE, van Horssen J. Differential expression of glucose-metabolizing enzymes in multiple sclerosis lesions. Acta Neuropathologica Communications. 2015; 3:79.205

25. Van Lith SAM, Navis AC, Lenting K, Verrijp K, Schepens JTG, Hendriks WJAJ, Schubert NA, Venselaar H, Wevers RA, van Rooij A, Wesseling P, Molenaar RJ, van Noorden CJF, Pusch S, Tops B, Leenders WPJ. Identification of a novel crippling mutation in isocitrate dehydrogenase 1 (IDH1R314C) in a high-grade astrocytoma. Scientific Reports. 2016; 6:30486.224

26. Edwards AL, Meijer DH, Guerra RM, Molenaar RJ, Alberta JA, Bernal F, Bird GH, Stiles CD, Walensky LD. Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides. ACS Chemical Biology. 2016; 11:3146-53.678

27. Khurshed M, Molenaar RJ, Lenting K, Leenders WPJ, van Noorden CJF. In silico gene expression analysis reveals glycolysis and acetate anaplerosis in IDH1 wild-type glioma and lactate and glutamate anaplerosis in IDH1-mutated glioma. Oncotarget. 2017; 8:49165-77.159

28. Le T, Leenders WP, Molenaar RJ, van Noorden CJF. Effects of the green tea polyphenol epigallocatechin-3-gallate on glioma: a critical evaluation of the literature. Nutrition and Cancer. 2017; in press.

29. Hira VV, Wormer JR, Kakar H, Breznik B, van der Swaan B, Hulsbos R, Tigchelaar W, Tonar Z, Khurshed M, Molenaar RJ, van Noorden CJF. Peri-arteriolar glioblastoma stem-like cell niches express bone marrow hematopoietic stem cell niche proteins. Journal of Histochemistry and Cytochemistry. 2017; in press.

Book chapters Karuntu J, Loncq de Jong M, Molenaar RJ, Oncology, in: Compendium Geneeskunde (Compendium Medicine) Editors: Smit V, Snijders R, 2016, Rotterdam, The Netherlands. Other publications

1. Molenaar RJ. De coschappen zitten vol. Het Parool, 9 February 2010. 2. Molenaar RJ and van den Doel R. Kabinet moet uitzoomen bij bezuinigingen op het hoger onderwijs.

NRC Next, 21 January 2011. 3. Molenaar RJ and Bijvank FA. Kenniseconomie heeft baat bij bredere studies. Trouw, 5 November

2015.

Clinical trial protocols 1. Molenaar RJ, Coelen RJ, Gelderblom AJ, van Gulik TM, Wilmink JW. Phase Ib study of metformin and

chloroquine in IDH1/2-mutated solid tumours (MACIST), 2015. 2. Molenaar RJ, Bins AD, de Reijke TM, Wilmink JW. Phase II study of oral metformin for intravesical

treatment of non-muscle-invasive bladder cancer (TROJAN), 2017.

Software packages Radivoyevitch T, Molenaar RJ. SEERaBomb: an R package to use SEER and A-bomb survivor data with R. Github (https://github.com/radivot/SEERaBomb) 2015-present. 5. Other Peer reviewer for: Academic journals: Journal of the National Cancer Institute, Cancer Research, Journal of the American Chemical Society, Oncotarget, Journal of Biological Chemistry, Acta Neuropathologica, Acta Neuropathologica Communications, Neuro Oncology, Journal of Neurooncology, International Journal of Cancer, Journal of Histochemistry & Cytochemistry, BMC Neurology, Mini-Reviews In Medicinal Chemistry, Vascular Health and Risk Management, Experimental & Molecular Pathology, Current Molecular Pharmacology, Journal of Bone Oncology, Journal of Cancer Biology & Treatment, Open Journal of Clinical & Medical Case Reports. Funding agencies: European Research Council (2015).

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Appendix: Authors and affiliations

Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Dept. of Experimental Surgery Coelen RJ, van Gulik TM, Roos E Dept. of Medical Biology Botman D, Dimitrakopoulou D, Hira VV, Khurshed M, van

Noorden CJ, Smits MA, Stap J, van de Venne T Dept. of Medical Oncology Bins AD, Meeuwisse A, Klümpen HJ, van Laarhoven HW, van

de Venne T, Wilmink JW Dept. of Neurosurgery Vandertop WP, Verbaan D Dept. of Otorhinlaryngology van Drunen CM Dept. of Orthopaedic Surgery Bramer JA Dept. of Pathology Hulsebos TJ, Troost D Dept. of Pharmacology Mathôt RA Dept. of Radiation Oncology Hulshof MC, Machiels M Dept. of Radiology Caan MW VU University Medical Center, Amsterdam, The Netherlands Dept. of Medical Oncology Van Linde ME Dept. of Neurology Kouwenhoven M Dept. of Neurosurgery Vandertop WP Dept. of Pathology Wesseling P Radboud University Medical Center, Nijmegen, The Netherlands Dept. of Cell Biology Hendriks WJ Dept. of Radiology and Nuclear Medicine

Heerschap A, Peeters TM

Dept. of Radiotherapy Span PN Dept. of Pathology

De Bitter T, Boots-Sprenger SH, Jeuken JW, van den Heuvel CN, Leenders WP, Lenting K, van Lith SA, Navis AC, van Tilborg AA, Tops B, Verrijp K, van de Water C

Dept. of Neurosurgery Ter Laan M Cleveland Clinic, Case Western Reserve University, Cleveland, OH, United States Dept. of Cardiovascular Medicine Hazen S Dept. of Endocrinology, Diabetes and Metabolism

Nasr C

Dept. of Haematology & Oncology Adelstrein DJ, Advani AS, Angelini D, Carraway HE, Gerds AT, Hill BT, Kalaycio ME, Majhail NS, Mukherjee S, Nazha A, Sekeres MA

Dept. of Radiation Oncology Godley A Dept. of Quantitative Health Sciences

Radivoyevitch T

Dept. of Translational Hematology & Oncology Research

Abdel-Hamid ON, Clemente MJ, Hirsch CM, Hosano N, Maciejewski JP, Makishima H, Kha BH, Kuzmanovic T, Lindner D, Nagata Y, Patel B, Przychodzen B, Sanikommu SR, Thota S

Mayo Clinic, Rochester, MN, United States Dept. of Haematology & Oncology Sidana S

Appendix: Authors and affiliations

252

National Cancer Institute, Bethesda, MD, United States Dept. of Haematology & Oncology Pleyer C Memorial Sloan-Kettering Cancer Center, New York, NY, United States Dept. of Medicine Viny AD Netherlands Cancer Institute, Amsterdam, The Netherlands Family Cancer Clinic Bleeker FE Leiden University Medical Center Dept. of Pathology van den Akker BE, Bovée JV, Cleton-Jansen AM, Cleven AH, de

Jong Y, Kruisselbrink AB, Niessen B, Peterse EF Dept. of Medical Oncology Gelderblom AJ Munich Leukemia Laboratories, Munich, Germany Alpermann T, Haferlach T, Meggendorfer M Kyoto University, Kyoto, Japan Dept. of Pathology and Tumour Biology

Chiba K, Miyano S, Ogawa S, Shiraishi Y, Tanaka H

Imperial College London, London, United Kingdom Haematology Research Centre Gale RP University of California, Berkeley, CA, United States Dept. of Mathaemathics Sachs RK Columbia University, New York, NY, United States Dept. of Radiation Oncology Brenner DJ Miller School of Medicine, University of Miami, Miami, FL, United States Dept. of Biochemistry and Molecular Biology

Xu M

Ludwik Rydygier Medical University, Bydgoszcz, Poland Dept. of Clinical Biochemistry Olinski R Erasmus University Medical Center Dept. of Neurosurgery Leenstra S Luxembourg Institute of Health, Luxembourg, Luxembourg Dept. of Oncology Niclou SP University of Bergen, Bergen, Norway Dept. of Biomedicine Bjerkvig R Institute for Cancer Research and Treatment, University of Torino, Candiolo, Italy Dept. of Molecular Oncology Bardelli A, Lamba S, Zanon C

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Appendix: Curriculum Vitae

Remco J. Molenaar

• Geboren 6 april 1990, te Amsterdam

• Opleiding:

o 2008: Gymnasium behaald, Oostvaarders College (cum laude)

o 2009-2012: Honours’ Programme Geneeskunde aan het Academisch Medisch Centrum

o 2011: University of California-Berkeley, summer school (Biostatistics)

o 2012: Dana-Farber Cancer Institute & Harvard Medical School, onderzoeksstage

gesuperviseerd door prof. dr. Charles Stiles

o 2012: Harvard Medical School & Massachusetts General Hospital, summer school

(Biomarkers in Central Nervous System Diseases)

o 2017: Artsexamen behaald aan het Academisch Medisch Centrum (cum laude)

o 2013-2017: promotieonderzoek, afdelingen Medische Biologie en Medische

Oncologie, Academisch Medisch Centrum

o 2017-heden: post-doctoral research fellow, Taussig Cancer Institute, Cleveland Clinic

• Extracurriculair:

o 2009-2010: Facultaire Studentenraad AMC, voorzitter

o 2015-2016: Facultaire Studentenraad AMC, coassistent

o 2015-2016: CoRaad AMC, algemeen lid

• Klinisch:

o 2017-heden: arts-assistent, afdeling Interne Geneeskunde, Flevoziekenhuis

• Hobbies:

o Hardlopen (marathon PR: 3 uur, 6 minuten)

o Fietsen (triathlon PR: 11 uur, 54 minuten)

o Saxofoonspelen

o Skiën (https://youtu.be/_fYNAW_HDMI)

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Appendix: Dankwoord Hoewel promotieonderzoek soms eenzaam is heb ik het gelukkig niet alleen hoeven doen, integendeel. Ten eerste mijn promotoren, prof. dr. C.J.F van Noorden en prof. dr. W.P. Vandertop. Waarde Ron, waarde Peter, gaandeweg is mijn proefschrift en het aantal onderwerpen behoorlijk gemetastaseerd. Dit was nooit mogelijk geweest zonder jullie zegen en vrijheid. Ron, jij hebt mij altijd gestimuleerd om over de schutting te kijken om dingen te leren die ik nog niet kan. Zonder die instelling was dit proefschrift een heel stuk later en een heel stuk dunner afgekomen. Mijn co-promotoren, dr. F.E. Bleeker en dr. J.W. Wilmink. Beste Fonnet, beste Hanneke, in een soort estafette hebben jullie mij naast jullie klinische taken begeleid, waar ik jullie zeer dankbaar voor ben. Jullie hebben me geleerd wat klinisch nuttig onderzoek is, dat is de meest waardevolle les die er is. Dank aan jullie allen voor de steun in de soms stroeve aanloop naar mijn proefschriftverdediging. Leden van de leescommissie, professoren Bossuyt, Leenstra, van Oers, Punt, Stalpers en Würdinger, dank voor het lezen van mijn proefschrift, ik zie uit naar de verdediging. Ook een grote dank aan de leden van de AMC Graduate School, in het bijzonder professoren Sterk, Büller, Fliers, Geijtenbeek, de Vries en dr. Stouthard voor het in mij gestelde vertrouwen en het AMC PhD Scholarship. Dit heeft mij de vrijheid gegeven om dit proefschrift (en alle studies die er niet meer in pasten) op mijn eigen manier te schrijven en het meeste uit mijn promotietijd te halen. Mijn paranimfen, dokter van de Venne en dokter van der Lee. Beste Tim en Koen, het doet me veel dat twee van mijn beste vrienden naast mijn zijde staan op deze bijzondere dag. Het begeleiden van jullie wetenschappelijke stages was de leukste tijd van mijn promotieonderzoek. My earliest mentors, prof. dr. C.D. Stiles, dr. J.A. Alberta, and dr. D.H.M Meijer. Dear Chuck, John, and Dimphna, thank you for showing me how far hard work, creativity, and having fun gets you in science. My American mentors, colleagues and friends, prof. dr. J.P. Maciejewski, prof. dr. M.A. Sekeres, dr. S. Mukherjee, and dr. T. Radivoyevitch. Dear Jarek, dear Mikkael and dear Sudipto, thank you for your mentorship and all the good moments. Dear Tom, Kirsten and kids, this thesis would not have been possible without your science, R lessons, hospitality and friendship. I can’t tell you how grateful I am. Dank aan iedereen van de onderzoeksgroepen van dr. W.P.J. Leenders en prof. dr. J.V.M.G. Bovée. Beste William en Judith, het is inspirerend hoe enthousiast jullie altijd zijn over IDH1/2. Moge er nog vele KWF-projecten volgen. Dank aan alle stafleden, studenten en medewerkers van de AMC afdelingen Medische Biologie, Medische Oncologie en Radiotherapie, voor de leerzame tijd en de prettige samenwerking. In het bijzonder Wikky en collega-promovendi Vashendriya en Mohammed. Tot slot de persoonlijke sfeer. Ik bedank graag al mijn vrienden voor in sommige gevallen al meer dan twintig jaar hechte vriendschap en mij excuseren voor de vele tijd die in dit boekje zit. Ik ga niemand bij naam noemen, want ik heb zoveel lieve mensen om mij heen dat het risico te groot is dat ik iemand vergeet. Toch speel ik even vals bij het noemen van mijn huisgenoot: als jij zelf aan je boekje moet beunen betaal ik terug door voor ons te koken, en mijn beste vriendin: we gaan samen eieren gooien. Mijn familie, bedankt voor jullie niet-aflatende steun. Natuurlijk een paar mensen in het bijzonder: lieve opa en oma. Ik ben heel blij dat jullie vandaag aanwezig kunnen zijn. Lief zusje, liefde gaat door de maag en er is niemand die dat zo goed door heeft als jij. Lieve papa en mama. Jullie grapten dat als ik geen AMC-beurs zou krijgen, mama achter de kassa ging werken om mijn onderzoek te betalen. Dat was gelukkig niet nodig, maar het geeft aan hoe groot jullie steun is geweest tijdens mijn studie, mijn onderzoek en met alle andere dingen in het leven. Ik draag dit proefschrift graag op aan jullie.

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Appendix: List of PhD dissertations, Brain Tumour Center Amsterdam

Date Name Title 06-10-2005 Carla Verstappen Cancer therapy related neurotoxicity 09-28-2005 Maaike Vos Evaluation of reponse, toxicity and outcome in glioma

therapy 12-20-2005 Birgit Georger Conditionally replicative adenoviruses for the treatment of

malignant glioma and neuroblastoma 12-20-2005 Jacques Grill Gene therapy and virotherapy of brain tumohrs with

recombinant adenoviruses 06-19-2009 Fonnet Bleeker Mutational profiling of glioblastoma 11-24-2009 Philip de Witt Hamer Glioblastoma: between bed and bench 05-07-2010 Ingeborg Bosma Cognitive dysfunction in glioma; underlying mechanisms

and consequences 09-23-2010 Christian Badr Bioluminescence imaging in glioblastom: monitoring of

biological processes and novel therapeutics 11-08-2010 Linda Douw Neural networks in brain tumours; the interplay between

tumour, cognition, and epilepsy 06-10-2011 Sander Idema Improving oncolytic viral therapy for glioma 10-05-2011 Anneke Niers Novel biosensors for preclinical brain tumour analysis 07-03-2012 Viola Caretti Pioneering preclinical research in diffuse intrinsic pontine

glioma: towards new treatment strategies 10-29-2012 Leonora Balaj Exosomes: the biological messengers 02-08-2013 Marjolein de Groot Epilepsy in brain tumour patients; towards improved and

personalised treatment 06-04-2013 Edwin van Dellen Lesions in the connected brain; a network perspective on

brain tumours and lesional epilepsy 12-04-2013 Michiel Smits Micro-RNA and epigenetic signaling in glioma angiogenesis 12-11-2013 Eefje Sizoo The end-of-life phase of high-grade glioma patients; towards

a dignified death 06-17-2014 Dannis van Vuurden Innovative treatment targets in pediatric high-grade brain

tumours 01-07-2015 Lotte Hidding Treatment sensitisers for high-grade tumours 03-17-2015 Marc Jansen Diffuse Intrinsic Pontine Glioma: clinical aspects and

imaging 05-11-2015 Florien Boele Towards improving health-related quality of life in glioma

patients and their informal caregivers 09-30-2015 Johan Koekkoek Epilepsy in glioma patients; optimizing treatment until the

end of life 01-19-2016 Sjoerd van Rijn Functional molecular imaging of cancer development and

stem cell regeneration in the nervous system 03-24-2016 Hinke van Thuijl Molecular characterization of low-grade glial neoplasms 05-18-2016 Avanita Prabowo Molecular Features of long-term epilepsy-associated

tumours; focus on glioneural tumours 06-08-2016 Ronald Willemse Functional mapping of the sensorimotor cortex: clinical

studies with MEG and fMRI 06-21-2016 Sharyar Mir Novel treatment targets in high-grade brain tumours 07-01-2016 Femke Froklage The role of the blood-brain barrier in drug-resistance and

central neurotoxicity 11-03-2016 Thijs Crommentuijn Development of vector-based strategies against

glioblastoma 11-28-2017 Lot Sewing Diffuse Intrinsic Pontine Glioma: disease models and

translational research 11-28-2017 Sophie Veldhuijzen van Zanten Diffuse Intrinsic Pontine Glioma: a multi-facetted and global

view