Our research theme’s

The CGC.nl scientific program focuses on six research themes:

1. To use and develop new model systems from primary human tumors to study responses to cancer drugs

Team leaders: Hans Clevers and Jan Paul Medema

The Clevers group has developed novel growth conditions for primary cancer organoid cultures (PCOCs). We will use this technology and patient-derived xenograft (PDX) models to establish a 'living biobank' of tumor material for research.

2. To identify and understand the critical changes in tumors (driver mutations) and the causes of resistance by applying functional screens

Team leader: René Bernards

Synthetic lethality screens will be used as a powerful tool to determine the cause of drug failure and/or acquired tumor resistances.

3. To identify and analyze (epi)genetic alterations in cancers, and their contribution to drug responses

Team leaders: Alexander van Oudenaarden en Maarten van Lohuizen

Recent advances in DNA sequence analysis allow rapid genome-wide identification of genetic and epigenetic alterations in tumors.

4. To identify and understand network perturbations within tumors and in tumor-host-interactions

Team leaders: Hans Bos and Peter Friedl

Recent developments in mass spectrometry and single cell analysis by fluorescence microscopy allow rapid analysis of the major signaling networks that are affected in tumors. These signaling networks are targets for most “targeted drugs”, and intrinsic -or acquired drug resistance is frequently caused by cross-talk between the major nodes of the network. Understanding this cross talk is key to designing more effective drug combinations.

5. To identify and analyze causes of genetic instability and their consequence for drug responses and resistance

Team leaders: René Medema and Roland Kanaar

Instability of the genome is one of the main causes of cancer progression and acquired drug resistance. At the same time, genomic instability is a tumor-specific weakness that can be exploited therapeutically, which is the goal of this part of the program.

6. To identify critical drug combinations for personalized cancer treatment

Team leaders: René Bernards and Emile Voest

To this end clinical studies will be designed in which cancer genomic data as well as functional organoid data are used to guide the choice of treatment. The studies will be performed within the context of the Center for Personalized Cancer Treatment (CPCT; www.cpct.nl), a unique collaboration recently established between University Medical Center Utrecht, NKI and Erasmus MC for genome-based clinical studies. The activities of our consortium will form the basis for novel mechanism-based, rational design of drug combination trials for cancer, and will significantly contribute to improved life expectancy and quality of life for cancer patients.