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Project description of the research to be funded for brain cancer

Overcoming resistance to immune therapies

Dr. P.J. French, Erasmus MC

Immune-therapies are an exciting new treatment strategy for cancer patients that uses the body’s immune system to target the tumor. Although such therapies have proven highly effective for several cancer types, they don’t seem to be effective for brain cancer patients. The reason why immune-therapies are ineffective in low-grade brain tumors is probably that these tumors can prevent cells of the immune system to enter the tumor. In contrast, such cells are present in high-grade brain tumors, and these tumors, therefore, can prevent the activation of immune cells.

In this project, we will use the differences between low- and high-grade tumors to discover the programs that determine exclusion or (in-) activation of immune cells.

Recent technological advances have made it possible to analyze single cells within specific locations of the tumor. This single-cell level is important because a tumor consists of many different cell types, and each type may contribute differently to the exclusion and/or inactivation of immune cells. Our research will, therefore, be done by looking at differences between single cells within brain tumors and analyze which programs are responsible for the lack of response to immune-therapies. Our research will form an essential step to help design the treatment of brain tumor patients with immunotherapy.

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Project description of the research to be funded for breast cancer

Redirecting splicing programs to combat breast cancer metastasis

Prof. Bob van de Water, Leiden University

Problem description

Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer, but for much a higher percentage of breast cancer deaths. This is due to the frequent occurrence of distant metastases in various organs including lung, bone, and brain. This makes treatment of TNBC a profound clinical challenge. Understanding the underlying molecular mechanisms of metastasis is therefore an important research direction.

Splicing factors

The Bob van de Water research group have identified two genes that are essential in metastasis formation. These genes regulate so-called ‘splicing factors’ that splice DNA during DNA-replication and remove non-functional DNA-segments. The researchers think that altered splicing machinery contribute to the development of metastases.


Unravel the role of splicing factors in breast cancer motility and metastasis. This research will determine the therapeutic relevance of splicing factors to combat TNBC metastasis and improve patient outcome and quality of life.

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Project description of the research to be funded for respiratory system cancers

Improving Checkpoint Blockade Therapy with Highly Immunogenic Personalized Neoepitope Vaccines

Prof. Peter Katsikis – Erasmus MC Rotterdam

Despite progression in our knowledge of cancer and advancement in chemotherapy, radiotherapy, and surgery, the cure rates in lung cancer remain very low. Recently, immunotherapy with checkpoint inhibitors has greatly transformed cancer treatment for a number of malignant diseases, including lung cancer. However, not all patients with cancer benefit from this promising therapy. Only a minority of patients respond with long lasting benefit and patients can experience significant toxicity. Furthermore, resistance to therapy can emerge in patients that initially respond. This project will develop a personalized therapeutic cancer vaccine that greatly increases the efficacy of checkpoint inhibitors in cancer patients, prolong their survival and improve quality of life.

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Project description of the research to be funded for digestive system cancers

Additional Treatment for Isolated Local Pancreatic Cancer Recurrence using Stereotactic Body Radiation Therapy

Dr. Martijn Intven – UMC Utrecht

Pancreatic ductal adenocarcinoma (PDAC) currently is the third leading cause of cancer related mortality in the Western world. Standard treatment exists of surgery followed by adjuvant chemotherapy. Administration of (neo)adjuvant chemotherapy has resulted in prolonged disease-free survival and decreased recurrence rates. However, up to 80% of patients with primary PDAC still develop disease recurrence within two years after surgical resection.

The aim of this study is to investigate whether local treatment using Stereotactic Body Radiation Therapy in addition to standard chemotherapy improves survival after recurrence compared to chemotherapy alone. SBRT may provide the best chances for effective palliation of symptoms, a reduction of morbidity due to local disease progression, and increased survival in good quality of life.

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Project description of the research to be funded for endocrine system cancers

Integrative mechanobiology and genomics profiling of resistance patterns to foster novel therapeutics in pancreatic cancer

Dr. Elisa Giovanetti – Amsterdam UMC (location VUmc)

Problem description

Pancreatic cancer is a highly lethal disease that is notoriously resistant to chemotherapy. The tumour microenvironment plays an important role in the development of this resistance. For instance, tumours are able to stiffen their environment. This drives survival and growth of tumour cells. Little is known about the underlying mechanisms.


Investigate how pancreatic cancer cells stiffen their environment and how this affects growth and chemotherapy resistance. By unravelling this molecular machinery, the research team expects to identify new targets for the development of new therapeutic strategies with better outcome.

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Project description of the research to be funded for gynecological cancer

Exploring the role of serine metabolism adaptations in platinum resistant high grade serous ovarian cancer

Prof. Reuven Agami, Netherlands Cancer Institute

Problem description

High-grade serous ovarian carcinomas (HGS-OCs) account for 70% of all ovarian cancers. Patients with HGS-OCs are often diagnosed with advanced disease. Their estimated 5-year survival is less than 35%. Standard-of-care treatment consists of surgery and platinum-based chemotherapy. Although 85% of patients respond to this treatment, around 70% of the tumours become resistant to platinum. Median survival for patients with recurrent disease is less than 3 years. As platinum-resistance cannot be predicted, it represents a major challenge. It demands a deeper understanding of its biology, as well as the development of combination treatment strategies.


Amino acids are organic compounds used for the biosynthesis of proteins. Tumour cells need high levels of amino acids to grow. The Reuven Agami research group shows special interest in the amino acid serine. Based on preliminary results, they hypothesize that adaptations in serine metabolism of ovarian cancer cells might increase their survival potential after treatment, leading to resistance.


1) Unravel the link between serine metabolism and platinum resistance of HGS-OCs. Explore the underlying mechanisms through which serine levels may impact on resistance to platinum-based therapy; 2) Identify other metabolic vulnerabilities of platinum-resistant HGS-OCs; and 3) Provide preclinical evidence of the value of targeting such metabolic alterations to overcome platinum resistance. Hopefully the results can be used for suggesting new (combinatorial) treatments to increase cure rates and improve prognosis.

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Project description of the research to be funded for hematological cancers

On the origin of childhood leukemia: studying somatic evolution in human blood

Dr. Ruben van Boxtel, Princess Maxima Center for Pediatric Oncology

Problem description

The initiation and progression of cancer is thought to result from DNA mutations. These mutations allow cells to expand themselves uncontrollably. The accumulation of DNA changes in cells is thought to be a key factor for getting cancer. This explains why cancer is age-related and occurs more often in the elderly. However, children can also develop cancer. In fact, some cancers, such as leukaemia, are more common in children than in adolescents, even though their young cells have less mutations.


Identify the mechanisms through which cancer arises in children. By studying mutation accumulation and mutational patterns in blood of children with leukaemia, the researchers hope to identify the processes that contribute to the genesis and development of childhood leukaemia. Ultimately, this work may generate candidate targets for future drug development.

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Project description of the research to be funded for skin & eye cancers

Stimulation of anti-melanoma T cell responses using a versatile vaccination carrier that targets antigen to CD169-expressing antigen presenting cells

Professor Joke den Haan – Amsterdam UMC

The use of checkpoint inhibitors in metastatic melanoma has resulted in a significant increase of patients with long-term survival. However, still a significant percentage of patients does not respond adequately to the treatment and this is correlated with a lower T cell response to the tumor. The researchers will develop a vaccine to stimulate T cell responses: this may enhance the effects of checkpoint inhibitors, especially in patients with absent or low T cell responses. The outcome of this study will not only be relevant for melanoma patients, but may also benefit patients with other cancer types in which vaccination with tumor antigens may improve clinical responses.

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Project description of the research to be funded for urinary system cancers

Boosting hyperthermia-based anticancer treatments

Professor Roland Kanaar – Erasmus MC Rotterdam

Hyperthermia – temporary elevation of tumor temperature to 41-43 °C –is a powerful partner in combination therapy with chemotherapy and/or radiotherapy. It has a proven clinical track record in combination therapy for various types of cancer, including bladder cancer. The efficacy of hyperthermia is negatively affected by a number of factors, such as insufficient thermal dose, temporary nature of hyperthermia effects (resulting in a short therapeutic window) and thermotolerance (induction of a temporary resistance to subsequent treatments). These shortcomings call for improved hyperthermia and that’s exactly what the researchers in this project aim for: they propose to pre-clinically test strategies that enhance effects of hyperthermia. These strategies are designed to lead to improved therapy outcomes via multiple avenues: inducing stronger toxicity for cancer cells, while sparing non-heated healthy tissues; rendering hyperthermia treatments effective at decreased temperatures or shorter durations. Excellent connections with clinicians and infrastructure allow for a fast translation of research results to application for cancer patients.

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Project description of the research to be funded for complementary and alternative therapy

Make open Communication about evidence-based Complementary Medicine part of routine oncology practice

Dr. Sandra van Dulmen – NIVEL, Utrecht

Many patients with cancer who are treated in conventional oncology practice look for complementary and integrative medicine (CM) therapies to reduce the psychological and physical burden of their disease. CM (e.g. mindfulness, acupuncture, yoga and herbal supplements) helps these patients to cope with their disease and to increase their quality of life and wellbeing. However, the current lack of communication about CM and the potential adverse effects on patients’ health and quality of life, ask for a supporting communication tool to allow all patients equal access to safe and evidence-based CM. This participatory project seeks to explore and strengthen the conditions that enhance open communication, access and implementation of safe and person-centred use of evidence-based CM in oncology in general and in breast cancer in particular by developing a CM communication guideline (COMMON) and an accompanying toolbox with and for patients and health care providers.

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Project description of the research to be funded for cancer prevention

Stop ovarian CAncer; implementation of the opportunistic salpingectomy in the Netherlands

Dr. Joanne de Hullu – Radboudumc Nijmegen

Opportunistic salpingectomy (OS) refers to the removal of the salpinges without the ovaries during interventions for benign (gynaecological) disease. This project aims to fully implement OS in the standard clinical practice of gynaecologists in all hospitals in the Netherlands. OS can decrease the incidence of ovarian cancer. Recent research has shown that salpingectomy is both hormonally and surgically a safe procedure. In this project, the researchers will develop and test tools to support the implementation of OS. After a pilot in the region of Gynaecologic Oncology Centre Nijmegen, implementation will be introduced in the South-East of the Netherlands and subsequently in all Dutch hospitals.