Scientific Annual Report 2019 Scientific Annual Report 2019 Contents 2 Introduction 14 Board members Director of Research 18 Group leaders 18 Neil Aaronson 37 Kees Jalink 56 Hein te Riele 19 Reuven Agami 38 Jos Jonkers 57 Lonneke van de Poll 20 Leila Akkari 39 Marleen Kok 58 Winette van der Graaf 21 Regina Beets-Tan 40 Pia Kvistborg and Olga Husson 22 Roderick Beijersbergen 41 Tineke Lenstra 60 Uulke van der Heide 23 Jos Beijnen 42 Sabine Linn 61 Michiel van der Heijden 24 André Bergman 43 René Medema 62 Wim van Harten 25 René Bernards 44 Gerrit Meijer and 63 Flora van Leeuwen and 26 Christian Blank Remond Fijneman Matti Rookus 27 Eveline Bleiker 46 Daniel Peeper 65 Fred van Leeuwen 28 Gerben Borst 47 Anastassis Perrakis 66 Maarten van Lohuizen 29 Thijn Brummelkamp 48 Benjamin Rowland 67 Jacco van Rheenen 30 Karin de Visser 49 Sanne Schagen 68 Bas van Steensel 31 Elzo de Wit 50 Alfred Schinkel 69 Olaf van Tellingen 32 William Faller 51 Marjanka Schmidt 70 Emile Voest 33 John Haanen 52 Ton Schumacher 71 Jelle Wesseling 34 Hugo Horlings 53 Titia Sixma 72 Lodewyk Wessels 35 Heinz Jacobs 54 Jan-Jakob Sonke 73 Lotje Zuur 36 Jacqueline Jacobs 55 Arnoud Sonnenberg 74 Wilbert Zwart 78 Division of 84 Division of 90 Division of Diagnostic Oncology Medical Oncology Surgical Oncology 96 Division of 102 Division of 110 Technology Radiation Oncology Pharmacology Transfer Office and Biometrics 112 Research Facilities 126 Education in 134 Clinical Oncology trials 164 Invited 166 Research 194 Personnel speakers projects index Netherlands Cancer Institute Plesmanlaan 121 1066 CX Amsterdam The Netherlands www.nki.nl Scientific Annual Report 2019 Introduction It is my pleasure to present the 2019 Scientific Annual Report of the Netherlands Cancer Institute. In it, we hope to convey how we have contributed to improving the prospects Director of Research of cancer patients by integrating state-of-the-art fundamental research, translational René Medema research, and clinical research. When I sat down to write these introductory words, I found it as difficult as each year to select just a few research highlights out of the many, with the aim of giving an idea of what we have learned and accomplished in 2019. We have all worked so hard, published beautiful papers or started or finished innovative clinical trials. But then I pictured the last or penultimate slide of all our PowerPoint presentations: the one in which we acknowledge all the people who have contributed to our project. And once again I realized the importance of collaboration in cancer research. Here are some examples of our collaborative efforts in 2019. Collaboration between the lab and the clinic is part and parcel of daily life in our Comprehensive Cancer Centre, in which some 45 nationalities are represented. In 2019, this collaboration between individual researchers and oncologists has again resulted in new insights into the mechanisms of cancer and into new patient impact. Since the summer of 2019, all oncologists within our hospital have been participating in a new clinical study in which we investigate, as the first hospital in the world and in collaboration with the Hartwig Medical Foundation, whether whole genome sequencing of tumour DNA can be implemented in standard cancer diagnostics. Our lab and clinic also closely collaborate with our pharmacy. In 2019, we have been building a brand new pharmaceutical centre equipped with innovative facilities that include clean rooms for developing advanced cellular therapies. When this becomes operative, it will lead to an even more fruitful integration of our research labs, our clinical research and our pharmacy. In 2019, the NKI and the Dutch Cancer Society designed a new cooperation agreement, covering the next five years. It devotes an annual €16.8 million for research at the Netherlands Cancer Institute. The link between the Dutch Cancer Society and the Netherlands Cancer Institute is a strong one and goes back to 1951. The fact that the Dutch Cancer Society is supporting us for another five years with this level of funding attests to their strong confidence in our work. In the years to come we will be working towards three common goals: making the results of scientific research accessible to patients more quickly, making both new and existing drugs more readily available, and improving the quality of life of everyone facing cancer or dealing with its aftermath. We also highly cherish our collaboration with all Dutch universities, including their medical centres, where the vast majority of our group leaders have a chair. In 2019, in their inaugurals, our recently appointed professors presented exciting plans for multidisciplinary collaboration with their university colleagues, aimed at generating new knowledge not only about cancer but also about other diseases, new methodologies and technologies, or about the human immune system. Many of our group leaders are also affiliated with the Oncode Institute, which unites top cancer research groups within the Netherlands and enables new collaboration in various domains. In November 2019, for instance, our institute hosted the launch of the Patient Perspective Program, which connects patients and cancer survivors to Oncode labs or individual Oncode researchers. This should decrease the distance between Oncode 2 researchers and patients so they can explore, investigate and understand each other’s worlds. Clinical research has always been impossible without collaboration with many professional partners, including pharmaceutical companies, health insurance companies, health care authorities, policy makers and thousands of patients. Collaboration has always been key in large randomized studies, but it is also becoming increasingly important in generating critical mass in innovative studies aimed at personalized medicine. These are studies with small cohorts of patients who often have rare molecular tumour profiles. At the European level, Cancer Core Europe, in which seven leading cancer centers, including the NKI, have joined forces, is a case in point. Within the EU, preparations for Horizon Europe, the next Research and Innovation Framework Programme, are in full swing. We are proud and happy that Regina Beets- Tan, head of our Radiology department, has been selected by the European Commission to be a member of Horizon Europe’s Mission Board for Cancer. Also, by working together in EU-LIFE with 13 other leading life science institutes, we can raise a powerful voice to convince the European Commission of the importance of fundamental research for the future health and well-being of Europe and its citizens. Close collaboration is also required at a global level and our research groups collaborate with other groups all over the world. In 2019, the NKI signed a declaration of intent for collaboration in clinical research with the Sun Yat-sen University Cancer Centre, which is one of best comprehensive cancer centres in China. The year before, the Netherlands Cancer Institute already signed a collaboration agreement with the Renji Hospital in Shanghai for the training of postdocs. In the Netherlands, average five-year survival rates for cancer have been rising by 1% over the past years, and the percentage of patients alive five years after diagnosis is now 65%, according to the Netherlands Cancer Registry. This is good news. Journalists often ask us whether, at a certain point in time, we will have ‘conquered’ cancer or have made it into a chronic disease. Our oncologists, who know from day- to-day experience that there are still many patients they cannot help, tend to be very modest. We also know that cancer will always be part of life, in an ageing society. FIGURE 1 CORE RESEARCH FUNDING THE NETHERLANDS CANCER INSTITUTE - ANTONI VAN LEEUWENHOEK HOSPITAL BY THE DUTCH CANCER SOCIETY AND THE MINISTRY OF HEALTH, WELFARE AND SPORT IN THE PERIOD 2007-2018 IN MILLION EUROS. 30 2012 2013 2014 2015 2016 2017 2018 2019 2011 2008 2009 2010 25 20 15 10 5 0 DUTCH CANCER SOCIETY MINISTRY OF HEALTH, WELFARE & SPORT* TOTAL * EXCLUDED ARE THE REIMBURSEMENTS FOR INTEREST AND DEPRECIATION OF BUILDINGS 3 And unfortunately, survival rates for certain cancers, such as ovarian and pancreas cancer are still depressingly low. And yet, in the Netherlands Cancer Institute, we believe that cancer need not be a terminal disease. We believe that within decades, cancer will have become a chronic disease that can be controlled, with good quality of life for the patients. We dare express this vision because we, as a global research community, are making steady progress in understanding the biology of cancer and in exploiting its Achilles heels. I am convinced that there are many more fundamental and practice-changing breakthroughs to come that will sooner or later benefit individual patients all over the world. However, whether we will be able to realize our vision partly depends on public investment in basic, curiosity-driven research. As I already mentioned, in 2019, the European Commission established the Mission Board for Cancer, as one of five mission boards established to help us solve our generation’s biggest challenges. This was a wise decision, in our opinion. But real health impact is not sustainable without strong and continued support for research aimed at understanding the fundamental mechanisms behind health and disease. Together with our partner institutes in EU-LIFE, we work hard to get this message along in Brussels. I end by thanking all our employees and everyone who supported us and collaborated with us in 2019. Since the foundation of the Netherlands Cancer Institute in 1913, we have received enormous support and commitment from our employees, volunteers and sponsors. I thank Tom de Swaan, who retired as chair of our supervisory board in 2019 and I welcome his successor Lodewijk Hijmans van den Bergh. I also want to thank the Dutch Cancer Society for their renewed institutional support and the Ministry of Health, Welfare and Sport for their substantial core funding.