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Molecular Pathology

Divisions

Groups within research area Molecular Pathology

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Jos Jonkers

Division
Molecular Pathology
Specialisation
Mouse Models of Breast Cancer

Introduction

Jos Jonkers began his scientific career at the NKI as a PhD student. He was drawn back in 2002 by the prospect of being able to rapidly translate basic research directly into clinical applications, and heads his own research group focusing on cancer. His group develops and utilizes sophisticated mouse models as critical tools to identify novel breast cancer genes and to learn how breast cancers grow and metastasize. They are also using them to test novel tumor intervention strategies that could improve treatment outcomes of breast cancer patients in the clinic.

More about the Jos Jonkers group

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Sabine Linn

Division
Molecular Pathology
Specialisation
Biomarker research

Introduction

In the clinic, we mainly use anticancer drugs based on outcomes of clinical trials that have been carried out in the general breast cancer population, whereas little is known about the molecular mechanisms underlying differential drug sensitivity. The same holds true for other cancer types, including gastrointestinal malignancies, and ovarian cancer. The focus of our research line is to unravel these molecular mechanisms in order to develop tests that may guide treatment decisions in the clinic and ultimately improve survival. For this purpose we use several genome-wide approaches and molecular techniques, in order to dissect the mechanisms that divide clinically well-defined cohorts of breast, gastrointestinal, and ovarian cancer patients into resistant and sensitive to a particular drug. We have a close collaboration with the groups of Jos Jonkers, Sven Rottenberg and Wilbert Zwart, who use conditional mouse models for breast cancer, derived clonal cell lines, and human cancer cell lines to study differential drug sensitivity in a controlled fashion.
A second research line focuses on the impact of prognostic molecular classifiers on adjuvant systemic treatment advice in breast cancer.

More about the Sabine Linn group

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Sven Rottenberg

Division
Molecular Pathology
Specialisation
Cancer Therapy Resistance

Introduction

Resistance to cancer therapy is a major barrier in clinical oncology. Most patients die from the presence of distant metastases that cannot be cured by standard treatments, and the development of resistance to a drug or other treatment can also occur at the primary tumor site. Sven Rottenberg studies cancer therapy resistance by focusing on mouse models that resemble breast cancer subtypes in humans. In these models, his group observes various ways in which cancer cells escape the deadly effects of classical chemotherapy, novel targeted drugs or radiotherapy, similar to the situation in cancer patients. Their goal is to identify mechanisms of resistance and test new approaches to avoid or reverse it.

This line of research is carried out in collaboration with the group of Jos Jonkers, and it continues a research branch of the Borst laboratory. Piet Borst is still linked to the Rottenberg group as adviser.

More about the Sven Rottenberg group

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Marjanka Schmidt

Division
Molecular Pathology
Specialisation
Breast cancer epidemiology

Introduction

Marjanka Schmidt came in 2002 to the NKI to work on breast cancer survival in patients with a BRCA1 or BRCA2 germline mutation. Her group was established in 2010 and focuses on the effects of genetic variants on risk, prognosis and long-term outcome of breast cancer. She also has an interest in the etiology of the development of specific breast cancer subtypes, which are strongly related to breast cancer outcome. Therapy and follow-up recommendations for breast cancer patients are based on the estimated average risk of tumor relapse and death, which is mostly based on tumor characteristics but not on patient genotype. Studying the impact of germline variants on the development of (contralateral) breast cancer subtype, treatment response and long-term survival, may eventually lead to inclusion of this information in guidelines or prediction tools for improved disease management, or in the pre-selection of women for breast cancer screening programs. We closely work together with treating clinicians, clinical geneticists, and molecular biologists. A second research line focuses on patient information and consent procedures, and return of results from research using human materials. This directly relates to the first research line as increasingly studies generate genetic information about hereditary variants. This research group is based in two divisions: Molecular Pathology, and Psychosocial Research and Epidemiology.

More about the Marjanka Schmidt group

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Jelle Wesseling

Division
Molecular Pathology
Specialisation
Breast Cancer Biomarkers

Introduction

Breast cancer is highly heterogeneous making it challenging to identify which individual patient needs additional treatment and, if so, what should be the most effective one. Therefore, Jelle Wesseling's work is focusing on optimizing personalized diagnosis and treatment of each breast cancer patient by searching for novel prognostic and predictive biomarkers. To identify such factors, his group uses a combination of pathology, molecular analyses, and epidemiology in four lines of research. First, his group has generated patient-derived xenograft models for human TNBC to test response and resistance development to systemic cytotoxic and targeted treatment and its relevance in the clinic. Second, they aim at developing clinical tests that can predict response on chemotherapy for locally advanced breast cancer by a variety of molecular methods. Third, he is involved in investigating factors determining radiosensitivity of breast cancer. Fourth, they try to find the balance between overdiagnosis and undertreatment of low-risk Ductal Carcinoma in Situ (DCIS). In addition, Jelle Wesseling is involved in complementary studies within and outside the institute, both nationwide as well as internationally.

More about the Jelle Wesseling group

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