Update on uveal melanoma: Translational research from biology to clinical practice (Review)

Abstract

Uveal melanoma is the most common type of intraocular cancer with a low mean annual incidence of 5-10 cases per million. Tumours are located in the choroid (90%), ciliary body (6%) or iris (4%) and of 85% are primary tumours. As in cutaneous melanoma, tumours arise in melanocytes; however, the characteristics of uveal melanoma differ, accounting for 3-5% of melanocytic cancers. Among the numerous risk factors are age, sex, genetic and phenotypic predisposition, the work environment and dermatological conditions. Management is usually multidisciplinary, including several specialists such as ophthalmologists, oncologists and maxillofacial surgeons, who participate in the diagnosis, treatment and complex follow-up of these patients, without excluding the management of the immense emotional burden. Clinically, uveal melanoma generates symptoms that depend as much on the affected ocular globe site as on the tumour size. The anatomopathological study of uveal melanoma has recently benefited from developments in molecular biology. In effect, disease classification or staging according to molecular profile is proving useful for the assessment of this type of tumour. Further, the improved knowledge of tumour biology is giving rise to a more targeted approach to diagnosis, prognosis and treatment development; for example, epigenetics driven by microRNAs as a target for disease control. In the present study, the main epidemiological, clinical, physiopathological and molecular features of this disease are reviewed, and the associations among all these factors are discussed. Contents 1. Introduction 2. Risk factors 3. Clinical manifestations 4. Anatomopathological study of uveal melanoma 5. Molecular classification of uveal melanoma: Genes involved 6. Uveal vs. cutaneous melanoma: Similarities and differences 7. Biology of uveal melanoma 8. Blood biomarkers for uveal melanoma 9. Proteomics and metabolomics in uveal melanoma 10. Clinical management of uveal melanoma 11. Conclusions and future directions

Uveal Melanoma Identified as Ocular Mass on Point-of-care Ultrasound

“…1 Prompt diagnosis of UM is clinically important because up to 50% of cases go on to develop distant metastases, 3 by which time mean survival drops to 6-12 months. 4 In patients with unilateral features such as ocular pain, vision loss, or elevated intraocular pressure, bedside ultrasonography plays a vital role in the diagnosis of intraocular masses.…”

The Analysis of Inflammation-Related Proteins in a Cargo of Exosomes Derived from the Serum of Uveal Melanoma Patients Reveals Potential Biomarkers of Disease Progression

“…The relapse and spread of the disease are highly correlated with poor prognosis, which in consequence results in only 8% of patients with metastatic UM surviving 2 years [3,4]. Currently, no effective therapies to prevent the development and treatment of metastatic disease are available, except for early detection and management of primary tumours [5,6]. Histological and genetic landmarks related to poor prognosis and increased risk of developing a metastatic disease in UM tumours have been described and tightly correlates with tumour size and chromosome 3 monosomy [3,7].…”

Artesunate combined with verteporfin inhibits uveal melanoma by regulation of the MALAT1/yes‑associated protein signaling pathway

“…As a common primary tumor in adults, uveal melanoma (UM) accounts for 3.7% of all melanomas ( 1 ). Numerous risk factors are associated with UM, including age, sex, genetic or phenotypic predisposition, work environment and dermatological conditions ( 2 ). UM has a strong propensity for fatal metastasis ( 3 ) and frequently metastasizes to the liver via the hematogenous route; according to data from 2005, 90% of UM metastases occur in the liver ( 4 ), which results in a dismal prognosis ( 5 ).…”

“…UM has a strong propensity for fatal metastasis ( 3 ) and frequently metastasizes to the liver via the hematogenous route; according to data from 2005, 90% of UM metastases occur in the liver ( 4 ), which results in a dismal prognosis ( 5 ). Additionally, severe inflammation has been identified in UM cells ( 6 , 7 ), particularly those with mutations of G protein subunit α (GNA)11 or GNAQ, which trigger a wide range of cell signaling cascades, including the PI3K/Akt/mTOR and YAP/TAZ pathways ( 2 ); however, limited approaches are available to alleviate inflammation in UM, as the eye is an immunologically privileged site, which provides UM with a protective niche ( 8 ). To date, several strategies have been adopted to treat UM in the clinic, including surgical resection, immunotherapy ( 9 ) and gamma knife radiosurgery ( 10 ).…”

“…To date, several strategies have been adopted to treat UM in the clinic, including surgical resection, immunotherapy ( 9 ) and gamma knife radiosurgery ( 10 ). For example, ipilimumab, an anti-cytotoxic T-lymphocyte-associated protein 4 antibody, elicits a positive response in 40–60% of patients with metastatic cutaneous melanoma ( 2 ), providing a potential new treatment for UM in the clinic. Recently, small molecules, such as selumetinib ( 11 ), nivolumab ( 12 ), ipilimumab ( 12 ) and selumetinib in combination with dacarbazine ( 13 ), have been identified as potential inhibitors of tumor progression able to improve the prognosis of patients with UM, although the underlying mechanisms remain elusive.…”