Research.

Lab for Cancer Predisposition and Precision Oncology

There is a 'can' in cancer because we CAN beat it!

Our Scope.

Through translational research we aim to contribute to the prevention, early diagnosis and treatment of cancer. We are running projects on germline cancer predisposition, with a major interest in gynecological tumors, pancreatic cancer and primary immunodeficiencies (PIDs).

We study DNA repair mechanisms, involved in cancer (predisposition). Zebrafish is applied as a model organism to set up assays for in vivo functional assessment of variants of unknown clinical significance in DNA repair genes.
For early detection of cancer and therapy monitoring studies on liquid biopsies are ongoing. Furthermore, we are setting up a zebrafish xenograft platform to predict tumor response to treatments. 

Cancer Predisposition.

It is estimated that about 5-10% of tumors have a familial background. Familial or hereditary cancer is the consequence of germinal alterations (mutations) in specific genes that increase the susceptibility to develop a malignant tumor. There are however still many variants of which the pathogenicity is unknown. In addition, many families are unaware that they have an inherited predisposition to cancer. A key example of this is in primary immunodeficiency disease (PID) families.
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Mission
Our mission is to unravel the genetic basis of (inherited) cancer.
Specifically, we aim:

• to gain insight in the genetic basis of patients with a presumed genetic predisposition for pancreatic cancer.
• to establish a minimally-invasive approach for adequate diagnosis and therapy monitoring of patients with pancreatic cancer. ​ ​
• to develop an in vivo functional assay to determine pathogenicity of variants of unknown clinical significance in BRCA2 and ATM.
• to unravel genetic factors contributing to cancer predisposition in primary immunodeficiency disease (PID) patients.

Strategy

• To research the genetic basis of inherited pancreatic cancer we analyse a custom designed targeted panel of cancer susceptibility genes. 
• We investigate the feasibility to detect both genomic rearrangements and point mutations in the blood of pancreatic cancer patients.
• The zebrafish model is utilized to insert human BRCA2 and ATM variants in their genome. This is done by Crispr-Cas9 mutagenesis. Functionality of these variants are subsequently tested.
• To gain insight into the predisposition to cancer in primary immunodeficiency disease patients we analyse a DNA damage response gene panel in whole exome sequencing data and targeted RNA sequencing data.

Precision Oncology.

Many cancers are still treated based on a 'one-size-fits all' principle. In addition, many treatments follow different lines of therapy upon relapse. However, these standard approaches are not always the best option for each individual patient. There is a great need for a personalized treatment tailored to in each patient's tumor. 

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​Mission
Our mission is to enable patient centered treatment, by:

• utilizing zebrafish as an 'avatar' for patient derived cancers.
  These cancers behave similarly to human cancer and are therefore ideal to test several treatment options at once and propose the best treatment options for each individual patient.
• combining both genetic and histopathological factors for optimal subtyping in ovarian cancer and their influence on prognosis.

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Strategy

• ​​Patient derived tumor material is engrafted into zebrafish embryos. For now, we focus on the development of ovarian and pancreatic PDX models in zebrafish.​ Upon successful engraftment, these embryos are treated with a wide range of (combination) treatments. Tumor responses will be analyzed and our suggestions could help to decide which treatment a patient's tumor is most likely to respond to and therefore increase the chance of an optimal treatment outcome.
• ​Starting from retrospective histopathological defined ovarian cancer types, we try to contribute to diagnostic precision by genomic profiling. For this purpose we analyse a targeted panel of genes to find both germline and somatic mutations. With these findings we hope to improve treatment selection in a prospective cohort of patients.

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Cooperation Partners.

Prof. Dr. Miguel Godinho Ferreira (Institute for Research on Cancer and Aging, Nice)
​Dr. Rita Fior (Champalimaud Centre for the Unknown, Lisbon)
MetaCell

Interested to work with us?

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Research Funding.