Development of new therapeutic options for the treatment of uveal melanoma. (1st May 2021)

• Record Type: Journal Article
• Authors: Wang, Janney Z.; Lin, Vivian; Toumi, Elsa; Wang, Ke; Zhu, Hong; Conway, R. Max; Madigan, Michele C.; Murray, Michael; Cherepanoff, Svetlana; Zhou, Fanfan; Shu, Wenying
• Is Part Of: FEBS journal. Volume 288:Number 21(2021)
• Page Start: 6226
• Page End: 6249
• Publication Date: 2021-05-01
• Subjects: C‐met inhibitors -- drug therapy -- EGFR inhibitors -- HDAC inhibitors -- immunotherapy -- MEK inhibitors -- uveal melanoma; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15869
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Important cytogenetic and genetic risk factors for the development of UM include chromosome 3 monosomy, mutations in the guanine nucleotide‐binding proteins GNAQ/GNA11, and loss of the BRACA1‐associated protein 1 ( BAP 1 ). Most primary UMs are treated conservatively with radiotherapy, but enucleation is necessary for large tumours. Despite the effectiveness of local control, up to 50% of UM patients develop metastasis for which there are no effective therapies. Attempts to utilise the targeted therapies that have been developed for the treatment of other cancers, including a range of signal transduction pathway inhibitors, have rarely produced significant outcomes in UM. Similarly, the application of immunotherapies that are effective in cutaneous melanoma to treat UM have also been disappointing. Other approaches that have been initiated involve proteasomal inhibitors and histone deacetylase inhibitors which are approved for the treatment of other cancers. Nevertheless, there have been occasional positive outcomes from these treatments in UM. Moreover, combination approaches in UM have also yielded some positive developments. It would be valuable to identify how to apply such therapies efficiently in UM, potentially via individualised tumour profiling. It would also be important to characterise UM tumours to differentiate the potential drivers of progression from those in other types of cancers. The recent identification of novel kinases and metastatic genes in UM tumours makes the development of new UM‐specific treatments feasible. Abstract : Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite the effectiveness of local control, up to 50% of UM patients develop metastasis for which there are no effective therapies. Attempts to utilise cytotoxic drugs, small molecules, signaling pathway modulators, receptor ligands and immunotherapies have been disappointing. The recent identification of kinases and genes involved in metastasis of UM offers the opportunity to develop new UM‐specific treatments.