Northern Netherlands Oncology Center (NNOC)

Research programme

Mission statement
The aim of the NNOC is to translate more fundamental insights in oncogenesis and tumor behavior from basic research into cancer prevention, improvement of early detection of cancer, and better treatment for cancer patients.

Aims for the four sub-programs:
1 Cancer: genes, mutations and their consequences

To study cancer susceptibility genes and mutations in these genes, and their direct and indirect involvement in cancer development.
To use genetic variation to identify and elucidate molecular pathways that characterize normal and aberrant cell development.

2 Hematopoietic development and hemato-oncology

To obtain detailed knowledge about molecular and other mechanisms that determine hematopoietic stem cell renewal and differentiation, with the ultimate goal of deepening our insight into the development of leukemia.
To obtain insight into the pathogenesis and evolution of B-cell lymphomas and Hodgkin lymphoma, and to find new tools for diagnosis and targets for therapy.

3 Translational Oncology

To explore new tools outlined in fundamental research, for innovative classification and diagnostics of cancer.
To identify new targets, outlined in fundamental research for innovative cancer therapy.

4 Clinical studies

To perform phase I, II and III studies in patients with solid tumors and patients with hematological malignancies in order to improve the treatment results.
To detect and prevent short-term and long-term side effects of cancer treatment.

Research area
Research is performed at the fundamental, translational and clinical levels. Central to the research is the goal of translating fundamental findings into practice in the clinic and vice versa. Therefore, there is a strong interaction between the research foci. The research foci of the four main sub-programs are:

1 Cancer: genes, mutations and their consequences
The detection of cancer-related gene alterations has proven successful in providing powerful diagnostic tools, and is often used for making decisions in clinical management. So far, most studies have focused on single gene alterations. However, with the elucidation of the human genome and the introduction of new technologies, thousands of genes can be screened simultaneously. This will result in new tumor markers or clusters of markers, which might help us to improve our understanding of cancer and our treatment of cancer patients. The aim of our studies is not only to identify such multiple gene alterations, but also to understand the cell biological effects of these alterations. More basic questions in our research program are related to genomic stability, the genes involved in maintaining this stability, the role of quantitative trait loci, and their relationship to cancer development. We exploit induced and naturally occurring genetic variation in order to identify and elucidate molecular pathways that characterize normal and aberrant blood cell development. We use high-end bioinformatics tools to detect and visualize genetic transcriptome
networks.

2 Hematopoietic development and hemato-oncology
An important aspect in understanding malignant deregulation in the hematopoietic compartment is the knowledge of the regulatory pathways that control the normal proliferation, differentiation and cell survival of young and aged hematopoietic stem cells. By making use of hematopoietic cells isolated from human cord blood and bone marrow, we are able to perform gene function analysis utilizing various strategies, including retro/lentiviral transduction protocols, RNAi approaches and multicolor flow cytometry. These protocols have also been optimized for acute myeloid leukemia (AML) cells of patients, which also provides the opportunity to study the gain of functions in the malignant counterpart.
For B-cell lymphomas and Hodgkin lymphoma, recent studies have shown that a distinction of real biological entities and determinants is essential for further improvement in targeted therapy and the clinical outcome of cancer. Although many lymphomas are characterized by primary genetic lesions, it is evident that additional genetic and epigenetic features, as well as mutations and polymorphisms of immune regulatory genes that influence the interaction with the environment – in relation to EBV infection or not – are all instrumental in the behavior of tumor cells. MicroRNAs may be key players in the modification of the expression of a large number of genes that are essential in normal and
neoplastic B cells.

3 Translational Oncology
Current classification of cancer is still based largely on the morphology of tumor cells, while current cancer diagnostics (e.g. CT/MRI) are primarily based on visualization of the size and shape, and to a lesser extent, the composition of tumors. The identification of more cancer-specific cell biological changes in tumors and/or body fluids and their visualization should lead to improved classification, detection and imaging of cancer. In addition, these cancer-specific cell biological changes should also be exploited to identify unique targets for innovative therapy.

4 Clinical studies
A major challenge is the translation of preclinical data into phase I clinical studies. In addition, phase II studies followed by phase III studies will finally give a true evaluation of new treatment options. Often, more information is required to understand the nature of the different response patterns seen in patients. This requires side studies with a broad variety of techniques to define in more detail the pharmacokinetic analysis, tumor pathology and imaging techniques, etc. With the improving results of anti-cancer treatments and the increasing numbers of long-term survivors, the relevance of and knowledge about the pathogenesis of treatment-induced long-term (and short-term) morbidity is also increasing. This knowledge about the occurrence of side-effects will provide opportunities for tailoring potentially toxic treatment and/or guiding primary and secondary prevention strategies for serious side effects of cancer treatment.

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Contact
Programme leaders

Name: Prof.Dr. E.G.E. de Vries
Phone: +31 (0)50 361 4862
e-mail Prof. de Vries

Name: Prof.Dr. H.J. Hoekstra
Phone: +31 (0)50 361 2317
e-mail Prof. Hoekstra

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