Medico-scientific research in uveal melanoma

Key publications (selection)

Metastatic management

• Total tumor volume and growth rate at 3 months on MRI outperform baseline imaging and circulating tumor DNA for predicting survival of patients with metastatic uveal melanoma receiving tebentafusp – Diagnostic and Interventional Imaging, 2026

Minimal-invasive monitoring — ctDNA / biomarkers

• Circulating Tumor DNA Monitoring in Patients with Uveal Melanoma Using Mutation-Agnostic Multiplex Drop-Off ddPCR Assays – Analytical Chemistry, 2026

Predisposition genetics

• Prevalence of the Predisposing Gene MBD4 for Uveal Melanoma – JAMA Ophthalmology, 2026
• Genetic Background Predicts Uveal Melanoma Patients' Outcomes – Ophthalmology Science, 2026
   

Clinical trials and cohorts

• Survival of Patients With MBD4-Mutated Metastatic Uveal Melanoma Treated With Immune Checkpoint Inhibitors – Translational Vision Science & Technology, 2026
   

Clinical guidelines

• Uveal melanoma: ESMO-EURACAN Clinical Practice Guideline – ESMO Open, 2026

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