Is there scientific hope and research equity for this rare disease?
Half of us will suffer from cancer during our lifetime. However, the top 10 most common cancers – such as breast, lung, prostate, and bowel – make up less than 65% of all cases1. The remaining third of cancer cases are rarer and often less well-researched.
Uveal melanoma (UM) is a rare but aggressive form of cancer that originates in the uveal tract of the eye, which includes the iris, ciliary body, and choroid. Most cases of UM develop in the choroid, a tissue layer filled with blood vessels and are known as choroidal melanoma2. The global incidence of primary UM is approximately 8,000 – 10,000 cases annually3.
Despite its rarity, prognosis is often poor, due to its tendency to metastasize, particularly to the liver. Once it metastasizes there are few treatment options, and it is often fatal within one year4.
However, scientific advances are rapidly evolving, offering new hope for patients. Such breakthroughs include:
- New advanced clinicals trials focusing either on unique and high-precision molecules or on novel immunotherapeutic approaches, ranging from T-cell receptor (TCR) therapies to oncolytic viruses
- Breakthroughs in molecular and genetic biology, allowing precision diagnostics
- 3D models like patient-derived organoids (PDOs)
Molecular determinants play a crucial role in UM. Mutations in GNAQ/GNA11 are associated with tumor initiation, while the loss of the BAP1 gene is a significant prognostic marker for metastasis. High expression of CYSLTR2 has been linked to a higher risk of metastasis. By identifying these markers, clinicians can personalize treatment plans to better address the individual needs of each patient4. New decision enabling tools such as DecisionDx-UM from Castle Biosciences offer personalized prognostic insights promising better patient care for patients with UM.
3D models, specifically PDOs are revolutionizing research in UM. These organoids are grown from patient tissue, replicating the unique genetic and biological characteristics of an individual’s tumor. They provide more accurate and representative models of the disease, allowing researchers to study tumor growth and responses to treatments in a way that closely mimics the natural environment of the tumor. This leads to more personalized and effective treatment plans5. Institutions like the Mayo Clinic are developing biobanks of patient-derived organoids for UM, creating a valuable resource for ongoing research and drug development5.
Beyond 3D models, single-cell transcriptomic analysis of human tumors has shed light on the microenvironment composition in human UM, identifying two tumor subtypes: one characterized by immune cell infiltration and the other more immune-deserted. However, in the infiltrated subtype, dysfunctional and exhausted immune responses impair antitumor immunity, leading to a poorer prognosis. Immunotherapeutic strategies aimed at restoring immune function are currently being explored.6
Clinical trials are underway for high-precision molecules, which offer better targeting of key cancer targets whilst minimizing off-target effects to increase patient safety. iOnctura’s lead asset roginolisib is one such high-precision molecule. Roginolisib is an oral small molecule allosteric modulator of PI3Kδ. Its unique allosteric modulation modality makes it highly specific for PI3kδ over other isoforms, translating into an unprecedented clinical profile for this class of drugs.
Results from the Phase I study, DIONE-01 showed promising outcomes, including good long-term safety and a doubling of median overall survival compared to historical controls. Trial sites were recently activated for the Phase II study, OCULE-01 which will compare roginolisib to standard-of-care in metastatic UM.
As a pioneering biopharmaceutical company, we are committed to advancing health equity within the rare disease community by developing high-impact, precision therapies that extend the health span of patients.
It is hoped that our high-precision molecule roginolisib, along with other scientific and innovative advancements are paving the way for more effective treatments and improved outcomes for those patients with UM.
Sources
- World Cancer Research Fund. Worldwide cancer data. Worldwide cancer data | World Cancer Research Fund. Last accessed: 18.02.2025
- Genetic and Rare Disease Information Center. Uveal melanoma | About the Disease | GARD. Last accessed: 18.02.2025
- American Cancer Society. Key Statistics for Eye Cancer | Ocular Melanoma Incidence | American Cancer Society. Last accessed: 18.02.2025
- Jager, M.J.; Shields, C.L.; Cebulla, C.M.; Abdel-Rahman, M.H.; Grossniklaus, H.E.; Stern, M.-H.; Carvajal, R.D.; Belfort, R.N.; Jia, R.; Shields, J.A.; et al. Uveal Melanoma. Nature Reviews Disease Primers 2020, 6, 24.
- Dalvin LA et al. Novel Uveal Melanoma Patient-Derived Organoid Models Recapitulate Human Disease to Support Translational Research. Invest Opthalmol Vis Sci. 2024 65(13):60.
- Li K et al. Single-cell and bulk transcriptome analysis reveals tumor cell heterogeneity and underlying molecular program in uveal melanoma. Journal of Translational Medicine. 2020 22 (1020)
