Uveal melanoma (UM) is a rare tumour of the eye, characterised by a high propensity to metastasise in half of all patients, most frequently to the liver.,Although there are effective treatment options for the primary tumour, once metastasis has occurred prognosis is poor, with overall survival limited to months.,Currently, there are no effective treatments for metastatic UM, despite the tumour having a well-defined signalling pathway to which many therapies have been directed.,In an effort to develop novel treatment approaches, understanding the role of other signalling molecules, such as microRNAs, is fundamental.,MicroRNAs (miRNAs) are small non-coding RNA molecules involved in posttranscriptional gene regulation, resulting in reduced target gene expression and subsequent protein translation.,In UM, several dysregulated miRNAs have been proposed to play a functional role in disease progression, whereas others have been put forward as clinical biomarkers of high-risk disease following isolation from blood, plasma and exosomes.,Most recently, analyses of large datasets have identified promising prognostic miRNA signatures and panels.,This review navigates the plethora of aberrant miRNAs disclosed so far in UM, and maps these to signalling pathways, which could be targeted in future therapies for the disseminated disease.
Uveal melanoma (UM) is highly refractory to treatment with dismal prognosis in advanced stages.,The value of the combined checkpoint blockade with CTLA-4 and PD-1 inhibition in metastatic UM is currently unclear.,Patients with metastatic or unresectable UM treated with ipilimumab in combination with a PD-1 inhibitor were collected from 16 German skin cancer centers.,Patient records of 64 cases were analyzed for response, progression-free survival (PFS), overall survival (OS), and safety.,Clinical parameters and serum biomarkers associated with OS and treatment response were determined with Cox regression modelling and logistic regression.,The best overall response rate to combined checkpoint blockade was 15.6% with 3.1 and 12.5% complete and partial response, respectively.,The median duration of response was 25.5 months (range 9.0-65.0).,Stable disease was achieved in 21.9%, resulting in a disease control rate of 37.5% with a median duration of the clinical benefit of 28.0 months (range 7.0-65.0).,The median PFS was 3.0 months (95% CI 2.4-3.6).,The median OS was estimated to 16.1 months (95% CI 12.9-19.3).,Regarding safety, 39.1% of treated patients experienced a severe, treatment-related adverse event according to the CTCAE criteria (grade 3: 37.5%; grade 4: 1.6%).,The most common toxicities were colitis (20.3%), hepatitis (20.3%), thyreoiditis (15.6%), and hypophysitis (7.8%).,A poor ECOG performance status was an independent risk factor for decreased OS (p = 0.007).,The tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma.,This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.