Research

Introduction
Research programme 'Experimental Biology'
Research programme 'Experimental Clinical Research'
Research facilities

Introduction

Research carried out within the three OOA participating institutes has an excellent (inter)national status, as demonstrated by, amongst others the large number of research projects granted in open national and international calls, including several of the prestigious new cancer charity programme grants and ERC advanced grants. The faculty is strongly represented in the ‘vernieuwingsimpuls', the Veni-Vidi-Vici development grants for junior researchers and participates widely in CTMM projects and TI Pharma projects as well as in numerous EU integrated projects and networks of excellence. Funding also is strongly supported by the Dutch science foundation NWO and the cancer charity, KWF.

The OOA research program ranges from basic molecular biology of the cell to clinical bedside research; from fundamental studies on cellular signal transduction pathways and the control of gene expression to new clinical trials and the development of new methods to improve quality of life of cancer patients. Although improvement of cancer prevention, diagnosis and treatment is the ultimate goal of the collaborating institutes, considerable effort is devoted to the study of normal cells and normal developments. Without a thorough understanding of normal cells and cell-cell interaction, it is not possible to fully understand the abnormal behaviour of cancer cells.
In practice the OOA research program is divided in two main topics; Experimental Biology and Experimental Clinical Research.

Research programme Experimental Biology

Transformation of a normal cell into a malignant cell requires multiple (epi)genetic alterations affecting key genes controlling cellular pathways. Studying genes and proteins involved in these pathways results in better understanding of tumor development, progression and therapy resistance. Using innovative research tools, novel components of major cancer-relevant pathways are further unravelled. Tools applied in research projects include high-throughput methods for (epi)genetic, transcriptomic and proteomic analyses. Examples are large tumor cohort screens with CGH or expression arrays, gain-of-function genetic screens with retroviral cDNA expression libraries, and loss-of-function genetic screens with RNA interference libraries. Mechanistic studies using e.g. structural biology complement the functional studies. Advanced mouse models or sophisticated xenotransplant models have been developed for the genetic dissection of cancer. At cellular level, processes like cell-cell communication, adhesion, migration, survival, proliferation and differentiation are studied. Furthermore, mechanisms of therapy resistance and metastasis are being investigated. Viral oncogenesis projects focus on the role of human papilloma viruses and Epstein-Barr virus in the development of human cancer, by using both in vitro models and clinically well-defined patient tumor samples. Viral and host markers are being tested for their capability to assess the risk associated with the development of cancer.

Research programme ‘Experimental Clinical Research'

Improvements in clinical care in oncology originate in improved detection, better treatment and translation of basic science findings in the clinic. The emerging and rapidly growing fields of molecular imaging and genomics provide new opportunities to study the biology of a malignancy in individual patients and allows for development of highly valuable indicators for diagnosis and prediction of disease outcome. Development of the 70-gene breast cancer predictor at the NKI has lead to the first FDA approved diagnostic screen for breast cancer. Modern state-of-the-art techniques like CT, MRI, SPECT and PET enable imaging methods with high precision and unique molecular and biological information at the tissue level. Reporter probes are being developed and evaluated. Highly developed mouse models emulating human tumor growth are used to follow drug sensitivity in several types of cancer and for developing clinical strategies for imaging. High-throughput tools are applied to measure (epi)genetic alterations and improve disease classification, including expression micro-arrays and CGH arrays. Quantitative mass spectrometry is applied to search for proteins distinguishing diseased and disease-free states. Targeted cancer therapy, is yet another research focus. Patient-tailored therapy should ensure optimal treatment benefits. Projects include (pre)clinical evaluation the use of neoadjuvant treatment or the application of new molecular therapies and antiangiogenic agents against novel targets in tumor and its environment. Pharmacological optimization of conventional cytotoxic drugs is an important line of research, as are passage of the blood-brain barrier by drugs and development of immune therapy. New immunotherapeutic approaches are being investigated and the impact of vaccination is being explored. Clinical trials are evaluating gene therapy with focus on optimal targeting and improving viral vector efficacy.

Research facilities

Apart from excellent IT facilities, electronic learning environments and library facilities, the three participating institutes provide top notch state of the art research facilities in all areas relevant to the study of cancer. Continuously new initiatives are taken and innovative technologies developed and implemented. This often occurs in the context of research programs in which PhD students as well as master students, during their rotations, are actively involved. Substantial parts of the training programs are devoted to these new technologies and will actually provide the students with skills and expertise to apply these methods for the sake of their own research. As the students already can get access to these facilities during their rotations, they will be stimulated to consider these facilities for their own research proposals as well.

State-of-the-art facilities include: