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Group Kranenburg

As a tumor biologist my drive is to help unravel the biological principles that govern the formation of metastases in colorectal cancer, and those that govern response and resistance to therapy. My team is composed of basic researchers and clinicians working closely together in a true translational research program. Clinical problems guide the definition of basic research questions and – vice versa – we strive to assess the clinical relevance and potential impact of the generated results.

U-port

To generate better models of the disease, including the aspect of intra- and inter-tumor heterogeneity, we are routinely using patient-derived organoids (PDO). To stimulate organoid-based research and to further improve the technology we have recently initiated the Utrecht Platform for Organoid Technology (U-PORT). 

Research Interest

Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality. Mortality is almost exclusively due to the development of distant metastases, which occurs in approximately half of the patients. Diagnostic tools for identifying the patients at risk for developing metastasis and for predicting response to therapy are currently lacking. Furthermore, effective metastasis prevention therapies are not available, at least in part because the molecular mechanisms of metastasis formation are still poorly understood. In addition, more effective metastasis treatment protocols are urgently needed. 

 

Theme 1: Preventing metastasis formation

The goal of this theme is to identify key signalling pathways that cause liver metastasis formation in CRC. Based on the obtained results we design novel diagnostic tools to identify patients at risk for developing metastasis and couple this to the development of novel therapeutic strategies for metastasis prevention. The general aim is to prevent metastasis formation in selected high-risk patient populations by targeting minimal residual disease. The experimental approach involves analysis of patient-derived tumor tissue and the use of organoid cultures and mouse model systems for spontaneous metastasis formation. Novel therapeutic strategies that show anti-metastatic potential in the organoid/metastasis models are then selected to be tested in cancer patients that are pre-selected with the novel diagnostic tools. To this end we have designed ‘proof-of-concept’ studies aiming to provide in-patient evidence for anti-tumor drug activity.

 

Theme 2: Optimizing metastasis treatment 

Approximately half of all colon cancer patients develop distant metastases. In addition to devising metastasis prevention strategies (first theme) it is equally important to optimize metastasis treatment protocols. The aim of this theme is to develop therapeutic strategies that prevent tumor recurrence after surgical resection of liver metastases, and following radio-embolization and chemotherapy. We build on our observations that hypoxia signaling and increased stem cell capacity play a key role in driving tumor relapse. The experimental approach involves analysis of patient-derived tumor tissue and the use of organoid cultures and mouse model systems for tumor recurrence in the liver. ‘Treat and Resect’ protocols in late stage cancer patients allow us to evaluate drug effects on residual disease in cancer patients and to obtain ‘proof-of-concept’ for the effectiveness of the chosen new therapeutic approaches.        

 

Research Team

PhD students

  • Inge Ubink
  • Nicola Frenkel
  • Emre Kucukkose
  • Alexander Constantinides
  • Niek Peters
  • Emma Wassenaar
  • Lizet van der Waals
  • Liza Wijler
  • Layla El Bouazzaoui (U-PORT)
  • Susanna Poghosyan
  • Emerens Wensink
  • Esther Strating

  

Master students

  • Aristeidis Lentzas
  • Hedy te Rietmole

 

Post docs

  • Jamila Laoukili

  

Technicians

  • Danielle Raats
  • Andre Verheem
  • Susanne van Schelven

  

Co-PIs

  • Inne Borel Rinkes
  • Jeroen Hagendoorn
  • Miriam Koopman
  • Jeanine Roodhart
  • Sjoerd Elias

 

U-PORT

  • Anneta Brousali
  • Anne Snelting
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