What we do
About our project
Uveal melanoma (UM) is the second most common form of melanoma and is associated with a high risk of metastasis. As clinical practice increasingly favors eye-sparing, minimally invasive treatments, such as irradiation, the availability of tumor tissue for molecular analysis is greatly reduced. This presents a significant challenge for accurate risk stratification and ongoing monitoring, as traditional tissue-based methods for gene expression, mutation, or copy number analysis become less feasible.
To address this gap, our research focuses on the development and validation of minimally invasive, blood-based biomarkers—often referred to as “liquid biopsies”—for the detection, prognosis, and monitoring of UM. Our work leverages advanced techniques in metabolomics, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs), in combination with medical imaging, to provide new avenues for patient care.
Minimally invasive biomarker strategies, particularly those leveraging ctDNA, CTCs, and metabolomics, show significant promise for the future of UM management. By combining these approaches with imaging, clinicians can achieve more accurate, real-time insights into tumor biology and patient prognosis, ultimately improving outcomes and reducing uncertainty for patients. Ongoing and future large-scale studies will be essential to validate these findings and establish standardized clinical protocols.
To address this gap, our research focuses on the development and validation of minimally invasive, blood-based biomarkers—often referred to as “liquid biopsies”—for the detection, prognosis, and monitoring of UM. Our work leverages advanced techniques in metabolomics, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs), in combination with medical imaging, to provide new avenues for patient care.
Minimally invasive biomarker strategies, particularly those leveraging ctDNA, CTCs, and metabolomics, show significant promise for the future of UM management. By combining these approaches with imaging, clinicians can achieve more accurate, real-time insights into tumor biology and patient prognosis, ultimately improving outcomes and reducing uncertainty for patients. Ongoing and future large-scale studies will be essential to validate these findings and establish standardized clinical protocols.
Our research focus
Our vision is to integrate multiple minimally invasive modalities—combining blood-based biomarkers and advanced imaging—to improve detection, monitoring, and prognostication in UM. This approach aims to overcome the limitations of tissue-sparing treatments, enable better patient stratification, and facilitate timely inclusion in therapeutic studies, especially for metastatic UM.
Our pilot studies have evaluated several promising approaches:
Circulating Tumor DNA (ctDNA):
We have demonstrated that ctDNA is detectable in a subset of UM patients, particularly those with metastatic disease. The detection of chromosome 3 loss in ctDNA corresponded to high metastatic risk in 70% of metastatic patients, highlighting ctDNA’s potential as a non-invasive tool for risk profiling.
Circulating Tumor Cells (CTCs):
Using a multi-marker capture approach, we detected CTCs in patients with localized UM and with metastatic disease. CTC counts were significantly higher in metastatic cases and increased during fractionated stereotactic radiotherapy (fSRT), suggesting a window for molecular characterization. While CTC counts did not correlate with traditional tumor characteristics, these findings support further exploration of CTCs as a prognostic biomarker.
Metabolomics:
Untargeted metabolomics of peripheral blood revealed distinct metabolite patterns that can accurately distinguish UM patients from controls (AUC = 0.99). Although these patterns did not differentiate between high- and low-risk UM patients, pathway analysis indicated dysregulation of malignancy-associated processes, suggesting potential for early detection and screening.
Our pilot studies have evaluated several promising approaches:
Circulating Tumor DNA (ctDNA):
We have demonstrated that ctDNA is detectable in a subset of UM patients, particularly those with metastatic disease. The detection of chromosome 3 loss in ctDNA corresponded to high metastatic risk in 70% of metastatic patients, highlighting ctDNA’s potential as a non-invasive tool for risk profiling.
Circulating Tumor Cells (CTCs):
Using a multi-marker capture approach, we detected CTCs in patients with localized UM and with metastatic disease. CTC counts were significantly higher in metastatic cases and increased during fractionated stereotactic radiotherapy (fSRT), suggesting a window for molecular characterization. While CTC counts did not correlate with traditional tumor characteristics, these findings support further exploration of CTCs as a prognostic biomarker.
Metabolomics:
Untargeted metabolomics of peripheral blood revealed distinct metabolite patterns that can accurately distinguish UM patients from controls (AUC = 0.99). Although these patterns did not differentiate between high- and low-risk UM patients, pathway analysis indicated dysregulation of malignancy-associated processes, suggesting potential for early detection and screening.
Funds & Grants
UitZicht
Algemene Nederlandse Vereniging ter Voorkoming van Blindheid
Landelijke Stichting voor Blinden en Slechtzienden
Rotterdamse Stichting Blindenbelangen
Stichting Oogfonds Nederland
Combined Ophthalmic Research Rotterdam
Stichting Wetenschappelijk Onderzoek Oogziekenhuis
Stichting Riemerfonds voor Ooglijders
Prof. Dr. Henkes stichting
Algemene Nederlandse Vereniging ter Voorkoming van Blindheid
Landelijke Stichting voor Blinden en Slechtzienden
Rotterdamse Stichting Blindenbelangen
Stichting Oogfonds Nederland
Combined Ophthalmic Research Rotterdam
Stichting Wetenschappelijk Onderzoek Oogziekenhuis
Stichting Riemerfonds voor Ooglijders
Prof. Dr. Henkes stichting
Collaborations
Department of Medical oncology
Translational Cancer Genomics (TCG)
Department of pathology and Clinical Bioinformatics
Oncogenetic research – group
Erasmus MC Cancer Institute
Erasmus MC Rare Disease Center
Erasmus MC Center for Familial and Hereditary cancer
Translational Cancer Genomics (TCG)
Department of pathology and Clinical Bioinformatics
Oncogenetic research – group
Erasmus MC Cancer Institute
Erasmus MC Rare Disease Center
Erasmus MC Center for Familial and Hereditary cancer
Rotterdam Ocular Melanoma Center
Oogziekenhuis Rotterdam
Publications
https://pure.eur.nl/en/persons/emine-kili%C3%A7/publications/ and https://pure.eur.nl/en/persons/erwin-brosens/publications/
Our team
Erwin Brosens, PhD, Molecular Geneticist, Program Manager
Emine Kilic, MD, PhD, Ophthalmologist, Ocular Oncologist and Vitreoretinal Surgeon
Rob Verdijk, MD, PhD, Ophthalmic Pathologist
Natasha van Poppelen, MD, PhD, Ophthalmologist, Ocular Oncology
Serdar Yavuzyigitoglu, MD, PhD, Ophthalmologist, Ocular Oncology
Jolanda Vaarwater, Ing, Senior Technician
Mike Wu, MSc, PhD candidate
Fabiana Bassil, MD, MSc, PhD Candidate
Kiki Bals, MSc, PhD Candidate
Bianca de Graaf, Ing, Senior Technician
Anja Wager, MD, PhD, Clinical Geneticist
Barbara van Paassen, MD, PhD, Clinical Geneticist
Marieke van Dooren, MD, PhD, Clinical Geneticist
Frank Magielsen, Ing, Database Administrator
Emine Kilic, MD, PhD, Ophthalmologist, Ocular Oncologist and Vitreoretinal Surgeon
Rob Verdijk, MD, PhD, Ophthalmic Pathologist
Natasha van Poppelen, MD, PhD, Ophthalmologist, Ocular Oncology
Serdar Yavuzyigitoglu, MD, PhD, Ophthalmologist, Ocular Oncology
Jolanda Vaarwater, Ing, Senior Technician
Mike Wu, MSc, PhD candidate
Fabiana Bassil, MD, MSc, PhD Candidate
Kiki Bals, MSc, PhD Candidate
Bianca de Graaf, Ing, Senior Technician
Anja Wager, MD, PhD, Clinical Geneticist
Barbara van Paassen, MD, PhD, Clinical Geneticist
Marieke van Dooren, MD, PhD, Clinical Geneticist
Frank Magielsen, Ing, Database Administrator
