Cell & Tissue Models
Prediction of therapeutic response is crucial in preventing administration of ineffective cancer treatments. Many researchers at USP, including those within Oncode, use advanced cell (e.g., Single Cell Analysis) and tissue (e.g., organoids - U-PORT, HUB , CMOB) models to improve cancer diagnosis and treatment outcome.
All knowledge institutes at Utrecht Science Park have extensive expertise in 3D miniature models of tumors, organoids, that are grown in vitro from patient-derived tumor cells. These ‘mini tumors’, or organoids, offer realistic models for drug development and testing, resulting in more effective systemic cancer therapies.
Breakthroughs and impact
The development of cell and tissues models that serve as a living model to understand cancer mechanisms, select the most effective of existing systemic treatments, and find new treatment opportunities.
Drug-repurposing screen Colon Cancer
A drug-repurposing library is used to screen patient-derived organoids of colorectal cancer (CRC). A microscopy-based screen accurately scores drug-induced cell killing of 414 putative anti-cancer drugs. One of these drugs, vinorelbine, is consistently independent of RAS mutational status. Its combination with EGFR/MEK inhibition induces apoptosis at all stages of the cell cycle and shows tolerability and effective anti-tumor activity in vivo, setting the basis for a clinical trial to treat patients with metastatic RAS-mutant CRC.
Basic understanding of cell competition
Tumors depend on microenvironment interactions for colonization. Cell competition is crucial, defining tumor growth dynamics within this context. The UU-Science faculty use organoid-based 3D co-culture systems and integrate quantitative long-term microscopy with single cell transcriptomics to study cell competition on a molecular, cellular and population level. The goal is to understand cell competition's impact on varied tumor growth types, envisaging these insights as a catalyst for pioneering therapeutic approaches.
Veterinary patients as models of human disease
Naturally occurring cancers in companion animals, such as dogs, have unique translational value to understand and treat cancer in humans. Dogs share our environment, are immunocompetent and experience cancers akin to humans. Their tumors develop, metastasize, and respond to therapy similarly to human cancers. ACCEPTOR (Faculty of Veterinary Medicine) taps into the vast potential of veterinary patients, for impactful comparative oncology research and preclinical data gathering. Together with Princess Máxima Center veterinary-derived organoids are tested for pediatric cancer drugs.
Disease model for neuroendocrine tumors
Neuroendocrine tumors (NETs) are relatively rare tumors that can be slow-growing but aggressive and hard to treat. Recently, researchers from the Organoid Group (Hubrecht Institute) and the Rare Cancers Genomics Team (IARC/WHO) developed new models to study neuroendocrine tumors (NETs) based on organoids from patient cells. These organoids mimic the behavior of actual NETs and can therefore be used to study this type of tumor in the lab. “This allows us and other scientists to understand the biology of these tumors so we can hopefully find effective therapies.” Although further research is needed, the model already points to a new route of treatment for patients with pulmonary NETs.
Urinoids as model for Bladder Cancer
A recent study from the UMC Utrecht demonstrated that bladder cancer organoids can be cultured directly from urine. Researchers have established 12 so-called urinoid lines from 22 patients. These urinoids serve as a non-invasive platform that advances precision medicine in bladder cancer. They facilitate detailed study of tumor pathogenesis, allow for longitudinal monitoring of drug responses, and support therapy adaptation.
Human fetal brain as organoid model
Scientists from the Hubrecht Institute and the Princess Máxima Center developed a novel in vitro organoid culture system for fetal brain of different anatomical sites, preserving their original identity and generation of the defined extracellular matrix. CRIPR-Cas9 modulation demonstrated the usefulness of these models to investigate mechanisms involved in the development of brain cancer.
Next generation experts
Our responsibility includes educating and training the next generation of researchers to create a dynamic environment in which innovative science will continue contributing to an ever-improving outcome for our patients.
PhD programmes
Within the Graduate School of Life Sciences we offer the following PhD programme tailored to this goal.
Students can also visit our other PhD programmes or Master's programmes.