系统性BRAF/MEK抑制剂作为转移性结膜黑色素瘤的一种潜在治疗选择
Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma.
作者信息
Mor Joel M, Heindl Ludwig M
机构信息
Department of Ophthalmology, University of Cologne, Cologne, Germany.
出版信息
Ocul Oncol Pathol. 2017 Jul;3(2):133-141. doi: 10.1159/000452473. Epub 2016 Dec 8.
Abstract
AIM
In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma.
METHODS
The study provides a PubMed literature review.
RESULTS
Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy.
CONCLUSIONS
The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.
摘要
目的
在本综述中，我们概述结膜黑色素瘤与皮肤黑色素瘤之间的相似性以及BRAF/MEK联合抑制在黑色素瘤中的有效性，并讨论这些药物在结膜黑色素瘤中的适用性。
方法
本研究提供了一篇PubMed文献综述。
结果
结膜黑色素瘤与皮肤黑色素瘤在基因和表型上相关。在超过50%的病例中，这两种肿瘤通常都存在BRAF突变。转移性皮肤黑色素瘤的新靶向治疗包括对BRAF和MEK的选择性抑制。BRAF/MEK联合抑制彻底改变了转移性皮肤黑色素瘤的治疗方式，显著改善了患者的预后。虽然这些新物质在皮肤黑色素瘤的治疗中已得到广泛研究，但由于结膜黑色素瘤这种恶性肿瘤较为罕见，尚无类似的研究。
结论
BRAF/MEK联合抑制应用于转移性或不可切除的结膜黑色素瘤显示出改善患者预后的巨大潜力。需要进一步的研究来调查其假定的益处。
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本文引用的文献
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2
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PLoS One. 2016 Aug 2;11(8):e0160485. doi: 10.1371/journal.pone.0160485. eCollection 2016.
3
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Lancet Oncol. 2016 Sep;17(9):1248-60. doi: 10.1016/S1470-2045(16)30122-X. Epub 2016 Jul 30.
4
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5
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8
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J Invest Dermatol. 2016 Apr;136(4):829-837. doi: 10.1016/j.jid.2015.12.035. Epub 2016 Jan 22.
9
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10
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