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Medico-scientific research in uveal melanoma
Institut Curie is one of the world’s leading centers for ocular oncology and uveal melanoma (UM), combining high-volume clinical care, clinical research, and integrated translational research:
new UM patients per year
proton-treated ocular cases
first-line metastatic cases per year
First-in-human to phase III trials facilities including cell therapies.
National and international reference: Institut Curie coordinates the French ocular oncology network and is a top global recruiter in UM clinical trials (up to ~30% enrolment when involved).
Data and biospecimens: Institut Curie has >8,000 clinical records; >1,000 primary tumours, >200 liver metastases biobanked; >20 patient-derived cell lines and >40 PDX; prospective sera and ctDNA collections.
Uveal melanoma research topics
Institut Curie develops a wide range of research programs on the following topics:
Clinical trials
From first-in-human to phase III trials (tebentafusp, LXS196/IDE196, MEK pathway, next-gen immune therapies).
Genetics and genomics
Germline predisposition, oncogenic drivers, chromosome alterations, BAP1 function, dormancy of disseminated cells.
Immunology & immunotherapy
T-cell biology, tebentafusp, SF3B1 neoepitopes and vaccine concepts, immunomonitoring.
Radiation biology
Proton therapy outcomes, radiation maculopathy
ctDNA dynamics
One of our research programs, which integrates genomics and immunology and is funded by the American Department of Defense, is described here.
Expert seminars on uveal melanoma
MomentUM seminars: Institut Curie organizes seminars by renowned experts in the field of Uveal Melanoma, which are broadcast worldwide. More information can be found here.
ESMO 2025 presentation of the PLUME trial
The PLUME trial (NCT05282901) is presented by Dr. Manuel Rodrigues at ESMO 2025 (October 18th, 2025): A Phase II, monocentric, single arm trial evaluating the efficacy and safety of Pembrolizumab in combination with Lenvatinib in metastatic Uveal MElanoma Patients.
ESMO 2025 presentation of the cohort of patients treated with tebentafusp
This cohort is presented by Dr. Raphael Sanchez at ESMO 2025 (October 20th, 2025): Clinical and molecular outcomes of Tebentafusp in metastatic uveal melanoma (MUM) : A retrospective cohort of 168 patients
ESMO 2025 presentation of the results of the Early Together clinical Trial
The results of the Early Together clinical trial (NCT04728113) are presented at ESMO 2025 by Dr. Sophie Piperno-Neumann. This trial evaluates whether early introduction of palliative care provides a benefit in terms of meeting psychological needs and support at 6 months in metastatic uveal melanoma patients.
Key publications (selection)
Ocular management
- Long-term follow-up of circumscribed iris melanomas treated by proton beam therapy – Eye (Lond), 2025
- Radiation Maculopathy After Proton Beam Therapy for Uveal Melanoma: OCT-A alterations influencing visual acuity – IOVS, 2017
- Optical Density Ratio of Subretinal Fluid in Choroidal Melanomas Versus Choroidal Naevi – IOVS, 2023
- Higher Subfoveal Choroidal Thickness in Choroidal Melanomas Than in Choroidal Nevi – Retina, 2024
Metastatic management
- Tumour growth rate improves tumour assessment and first-line systemic treatment decision-making – Br J Cancer, 2022
- Iterative surgery and radiofrequency ablation of liver metastases: very long-term survivors – EJSO, 2019
- Replacement and desmoplastic growth patterns in UM liver metastases – J Pathol Clin Res, 2018/2020
- Preoperative staging of liver metastases by MRI and FDG-PET – EJSO, 2010
Minimal-invasive monitoring — ctDNA / biomarkers
- Prospective assessment of circulating tumor DNA under tebentafusp – Nat Commun, 2024.
Rapid ctDNA decline predicts response and survival, validating ctDNA as a dynamic non-invasive biomarker. - ctDNA as a Prognostic Factor in Resectable Hepatic Metastases – Ann Surg, 2023
- First detection of ctDNA in metastatic uveal melanoma – Clin Cancer Res, 2012
Predisposition genetics
- Uveal Melanoma within the Lynch Syndrome spectrum – JAMA Ophthalmol, 2025
- Meta-analysis of GWAS identifies new loci and population heterogeneity – HGG Adv, 2024
- Familial UM and germline MBD4 variants – JNCI, 2024
Defines MBD4 as a germline predisposition gene linked to hypermutator tumours and familial UM. - SMARCB1-deficient malignant melanocytic uveal tumours – J Pathol, 2025
Defines a novel neural-crest derived uveal tumour entity linked to germline SMARCB1 deficiency. - Functional variant rs452384 (NKX2.4 interactor) – Am J Hum Genet, 2022
Tumor genomics
- SF3B1 mutations alter branchpoint usage and splicing – Nat Commun, 2016
Mechanistic basis for aberrant splicing and shared neoepitopes in SF3B1-mutant UM. - Outlier response to anti–PD1 in germline MBD4 mutation – Nat Commun, 2018
First link between MBD4 deficiency, hypermutation, and exceptional immunotherapy sensitivity. - Evolutionary Routes in Metastatic Uveal Melanomas – Clin Cancer Res, 2019
- MBD4 deficiency is predictive of response to immune checkpoint inhibitors – Eur J Cancer, 2022
- Multi-omics comparison of malignant vs normal uveal melanocytes – Cell Rep, 2023
- Integrative analysis of four clinico-molecular subsets (TCGA) – Cancer Cell, 2017
Landmark TCGA analysis defining 4 molecular subtypes linking genotype, immune context and prognosis. - Hippo-independent activation of YAP by GNAQ – Cancer Cell, 2014
- EZH2 inhibition resistance independent of BAP1 – Nat Med, 2016
BAP1 function
- BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation – Nat Commun, 2019
- Modulating BAP1 expression affects ROS homeostasis, cell motility and mitochondrial function – Oncotarget, 2017
- Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status – Nat Med, 2016
Immunobiology
- Divergent local and systemic antitumor response in primary UM – J Exp Med, 2024
Shows discordant local vs systemic immune responses driven by chromosomal and immune context. - Immune landscape of primary UM and liver metastases – Br J Cancer, 2023
- SF3B1-mutant UM generates shared immunogenic neoepitopes – Cancer Discov, 2021
Demonstrates common T-cell–recognized neoepitopes, paving the way for SF3B1-targeted vaccines.
Clinical trials and cohorts
- Phase I trial of LXS196 (PKC inhibitor) – Br J Cancer, 2023
- AEB071 (PKC inhibitor) genomic profiling + clinical results – Mol Cancer Ther, 2020
- Nivolumab + ipilimumab in metastatic UM (real-life cohort) – Oncoimmunology, 2022
- Selumetinib + dacarbazine (SUMIT) – J Clin Oncol, 2018
Negative randomized phase III trial; confirms the limitations of MEK inhibition alone. - Tebentafusp vs investigator’s choice (pivotal trial) – NEJM, 2021
First demonstration of overall survival benefit in HLA-A*02:01–positive metastatic UM. - Three-Year Overall Survival with Tebentafusp – NEJM, 2023
Long-term follow-up confirming durable OS benefit; tebentafusp established as new standard.
Models & translational resources
- Patient-Derived Xenografts as personalized therapy avatars – Curr Oncol, 2023
- PDX recapitulate molecular features of human UM – Mol Oncol, 2013
- Nanobodies for mapping genetic heterogeneity in UM PDX – Pigment Cell Melanoma Res, 2017