Abstract
Uveal melanoma (UM), which is the most common cancer of the eye, was investigated in recent years by many teams in the field of biomedical sciences and eye clinicians. New knowledge was acquired on molecular pathways found to be dysregulated during the multistep process of oncogenesis, whereas novel therapeutic approaches gave significant results in the clinical applications. Uveal melanoma-affected patients greatly benefited from recent advances of the research in this eye cancer. Tumour biology, genetics, epigenetics and immunology contributed significantly in elucidating the role of different genes and related pathways during uveal melanoma onset/progression and UM treatments. Indeed, these investigations allowed identification of new target genes and to develop new therapeutic strategies/compounds to cure this aggressive melanoma of the eye. Unfortunately, the advances reported in the treatment of cutaneous melanoma have not produced analogous benefits in metastatic uveal melanoma. Nowadays, no systemic adjuvant therapy has been shown to improve overall survival or reduce the risk of metastasis. However, the increasing knowledge of this disease, and the encouraging results seen in clinical trials, offer promise for future effective therapies. Herein, different pathways/genes involved in uveal melanoma onset/progression were taken into consideration, together with novel therapeutic approaches.
Highlights
Uveal melanoma (UM) is a rare malignancy of the eye
A recent study showed that amplification of CNKSR 3, membrane-associated guanylate kinase interacting protein-like gene, which maps on chromosome 6q25.2, extended metastatis-free survival in a group of uveal melanomas with monosomy of chromosome 3 [28], Figure 1
Moore and colleagues [39,40], analysing whole-genome and whole-exome sequencing data from 136 patients with uveal melanoma from multiple cohorts, found a previously undescribed mutation in Cysteinyl leukotriene receptor 2 (CYSLTR2) encoding a p.Leu129Gln substitution. This mutation was founded only in samples lacking mutations in GNAQ, GNA11 and PLCB4, suggesting that these mutations activate the same pathway. These findings reveal an oncogenic role for CYSLTR2 in uveal melanoma through activation of Gαq signalling, and further suggest that Leu129Gln CysLT2 R may be a potential therapeutic target in UM
Summary
Uveal melanoma (UM) is a rare malignancy of the eye. It is the most common primary intraocular cancer in adults. Of patients, but less than 4% of them have detectable metastases at the time of diagnosis [4,5,6]. Many patients may have clinically-undetectable micro-metastasis at time of diagnosis, so the current trend is to consider uveal melanoma as a systemic disease [7,8,9]. Important research efforts are being addressed to develop effective adjuvant therapies in order to prevent metastatic disease, which may offer prophylactic systemic treatment. No systemic adjuvant therapy has been shown to improve overall survival (OS) or reduce the risk of metastasis. Cancers 2019, 11, 694 biological molecules underlying disease pathogenies and dissemination, as well as the development of tailored therapies
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