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Updated: Jul 12, 2025
Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography
Published on: December 2, 2022
Identifying biomarkers and novel therapeutic targets in uveal melanoma
Anja Wessely1,2,3, Elias A T Koch1,2,3, Julio Vera1,2,3
1Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Abstract:
Uveal melanoma (UM) is an orphan cancer despite being the most common eye tumor in adults. Patients often present to skin cancer centers for treatment of metastatic disease although there are significant genetic, biological, and clinical differences from cutaneous melanoma. The treatments most commonly used for metastatic UM are tebentafusp and combined immune checkpoint blockade, both of which yield low response rates and may be accompanied by high treatment costs and significant immune-related toxicities. Thus, it is of paramount importance to identify biomarkers and clinical profiles predictive of treatment response and to find novel therapeutic targets. The use of immune checkpoint blockade showed more favorable outcomes in patients with extrahepatic disease and normal levels of serum lactate dehydrogenase in a panel of retrospective studies, making its use more reasonable in this subgroup. To identify novel drug targets, we will analyze the expression and relevance of neural crest transcription factors in patient bio-specimens using next-generation nanopore sequencing. Computer algorithms and network-based analysis will facilitate the identification of druggable targets which will subsequently be validated in patient-derived short-term cell cultures. This approach will help to find novel and personalized treatments for UM.
Insights
Uveal melanoma (UM) treatments have low response rates. This study seeks to identify new drug targets and predictive biomarkers for personalized treatments in uveal melanoma patients.
Area of Science:
- Ophthalmology
- Oncology
- Genetics
Background:
- Uveal melanoma (UM) is the most common adult primary eye cancer, often presenting as metastatic disease.
- Current treatments like tebentafusp and immune checkpoint blockade show limited efficacy and significant toxicities.
- Identifying predictive biomarkers and novel therapeutic targets is crucial for improving UM patient outcomes.
Purpose of the Study:
- To discover novel therapeutic targets for uveal melanoma (UM).
- To identify biomarkers and clinical profiles that predict treatment response in UM patients.
- To develop personalized treatment strategies for uveal melanoma.
Main Methods:
- Retrospective analysis of immune checkpoint blockade outcomes in UM subgroups (extrahepatic disease, normal LDH).
- Next-generation nanopore sequencing to analyze neural crest transcription factor expression in patient samples.
- Bioinformatic and network-based analyses to identify druggable targets.
- Validation of identified targets in patient-derived cell cultures.
Main Results:
- Immune checkpoint blockade demonstrated more favorable outcomes in patients with extrahepatic disease and normal serum lactate dehydrogenase levels.
- Identification of potential druggable targets through analysis of neural crest transcription factors.
- Validation of identified targets in patient-derived cell cultures is planned.
Conclusions:
- Subgroup analysis suggests specific patient profiles may benefit more from current therapies.
- Targeting neural crest transcription factors presents a promising avenue for novel UM drug discovery.
- This research aims to pave the way for personalized and more effective treatments for uveal melanoma.
