Development of new therapeutic options for the treatment of uveal melanoma

Wang Janney Z.; Lin Vivian; Toumi ElsaWang KeZhu HongConway R. MaxMadigan Michele C.Murray MichaelCherepanoff SvetlanaZhou FanfanShu Wenying

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Development of new therapeutic options for the treatment of uveal melanoma

机译：Development of new therapeutic options for the treatment of uveal melanoma

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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.

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《The FEBS journal》 |2021年第21期|6226-6249|共24页
作者
Wang Janney Z.; Lin Vivian; Toumi ElsaWang KeZhu HongConway R. MaxMadigan Michele C.Murray MichaelCherepanoff SvetlanaZhou FanfanShu Wenying;
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作者单位

Univ Sydney, Sydney Pharm Sch, Fac Med & Hlth, Sydney, NSW, Australia;

Univ New South Wales, Fac Med, Sydney, NSW, Australia;

Jiangsu Inst Nucl Med, Minist Hlth, Jiangsu Key Lab Mol Nucl Med, Key Lab Nucl Med, Wuxi, Jiangsu, Peoples R ChinaZhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou, Peoples R ChinaSydney Eye Hosp, Ocular Oncol Unit, Sydney, NSW, AustraliaUniv Sydney, Save Sight Inst, Sydney, NSW, AustraliaUniv Sydney, Fac Med & Hlth, Discipline Pharmacol, Sydney, NSW, AustraliaSt Vincents Hosp, Dept Anat Pathol, SydPath, Darlinghurst, NSW, Australia;

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正文语种英语
中图分类生物化学;
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C; 8208; met inhibitors; drug therapy; EGFR inhibitors; HDAC inhibitors; immunotherapy; MEK inhibitors; uveal melanoma;

Development of new therapeutic options for the treatment of uveal melanoma

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