Uveal Melanoma

P1, N=17, Completed, Hasumi International Research Foundation | Active, not recruiting --> Completed | N=12 --> 17

P1, N=106, Recruiting, MonTa Biosciences ApS | N=69 --> 106 | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Mar 2027

Clinically, the bispecific T-cell redirection drug Tebentafusp has achieved a major breakthrough in metastatic uveal melanoma immunotherapy. This review systematically elucidates key driver gene mutations, chromosomal abnormalities, epigenetic alterations, and the unique immunosuppressive microenvironment of uveal melanoma, providing new insights into mechanisms of treatment resistance and guiding the development of innovative therapeutic strategies.

P2, N=44, Recruiting, Diwakar Davar | Trial completion date: Mar 2030 --> Sep 2030 | Trial primary completion date: Mar 2028 --> Sep 2028

This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management.

SETD2 deletion potentiates isochromosome formation across diverse cancers. Combinatorial targeting of MITF together with a previously identified synthetic lethal gene may benefit UVM patients harboring both chr3 deletion and 8q+.

Our integrative approach identifies CDH17 and HOXC13 as biologically relevant, stage-associated prognostic biomarkers in UM. These findings provide a foundation for mechanistic studies and potential translational applications, including therapeutic targeting and risk-stratified patient management.

P2, N=13, Terminated, Dana-Farber Cancer Institute | Active, not recruiting --> Terminated; This was a Simon two stage design trial that terminated after the first stage due to lack of response.

While the use of EXOs presents a promising option for ocular treatment application, several factors complicate actual clinical translation, including standardization of isolation, scalable manufacture, and regulatory issues. In general, EXO-based nanomedicine may be a promising new direction for precision therapy and regenerative ophthalmology with the increasing introduction of synthetic and bioengineered EXOs introducing precursor paving new avenues for clinically scalable and biologically customizable EXO therapeutics.

Key translational enablers include assay harmonization (PD-L1, TMB, ctDNA), evidence-tiered validation, and pragmatic clinical trials incorporating biomarker-driven endpoints. Addressing cost, accessibility, and data ethics will be essential for biomarker-guided precision oncology to become a sustainable clinical reality across diverse health systems.

Collectively, these results identify GPX4 as a context-dependent, tumor-cell-intrinsic regulator with prognostic and immunological relevance across cancers, supporting its potential as a biomarker and therapeutic vulnerability in selected tumor types. The online version contains supplementary material available at 10.1007/s13205-026-04733-y.

Importantly, BAP1 knockdown, alone or in combination with ionizing radiation, sensitized UM cells to senolytic agents, dasatinib and quercetin. In conclusion, our findings identify BAP1 loss as a driver of senescence and suggest that BAP1 -mutant tumors may benefit from senolytics treatment.