DNA damage response in tumours of patients with endometrial cancer

Aim of this project 

The project has four steps. A step should be completed before the next step is undertaken.

1. Developing a method to use fresh tumour tissue for genetic analysis;
2. Developing a method to measure DNA damage response in fresh tumour tissue;
3. Measuring DNA damage response in tumour tissue;
4. Ex vivo testing in fresh tumour tissue of the response to different therapies.

Spin-off 

If this method is shown feasible in endometrial cancer, it may be possible to develop a similar test in cervical and ovarian cancer.

Execution of the project 

Women treated for endometrial cancer will be asked to provide consent for the use of “left over” tumor tissues for developing a method to test treatment effects in the lab.

Impact on patient care

The participating women will not benefit from this study. Ideally, in the future, a patient-tailored therapy with the best perspectives is applied after a preclinical test on a tumour sample of an individual patient, thereby avoiding non-active therapies.

Phase 1. Culture tumour tissues

We will develop a method to keep fresh tumour tissue alive for a short period. Thin slices of tumour tissue will be tested in several culturing conditions. Viability of the cells is tested using various staining protocols routinely carried out at the Erasmus MC department of Molecular Genetics.

Phase 2. Developing a test to measure DNA damage response

Techniques already used in cell suspensions will be adapted for analyses in tissues.

Phase 3.  Relate DNA damage response to clinical outcome

The results from the DNA damage response (DDR) analyses will be compared with clinical information of the specific patient, i.e. disease-free survival, overall survival, response to certain therapies, immunohistochemical markers such as the hormone receptor status and somatic mutations in the tumour.

Phase 4.  Ex vivo testing of the response to several therapies in fresh tumour tissue.

Ex vivo, we will test the DDR following several therapies, such as PARP inhibition, radiotherapy and cytostatics. Eventually, we aim to develop a tool with which we can predict whether a patient will benefit from specific therapies selected on the basis of the DDR profile.

Collaboration within Erasmus MC

• Department of Gynaecologic Oncology
• Department of Pathology
• Department of Molecular Genetics

• Patricia Ewing
• Dik van Gent
• Ronald Kanaar
• Lena van Doorn
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• Marjolijn Ladan
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• Dineke Smedts
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