Recent developments in prognostic and predictive testing in uveal melanoma.
Recent developments in prognostic and predictive testing in uveal melanoma.
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DOI：
10.1097/icu.0000000000000051
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发表时间：
2014-05
影响因子：
3.7
通讯作者：
Harbour JW
中科院分区：
文献类型：
--
作者：
Field MG;Harbour JW
为评估葡萄膜黑色素瘤的预后和预测对靶向分子治疗的反应提供快速发展的方法的最新进展。评估葡萄膜黑色素瘤预后的技术已经从简单的物理特征，如肿瘤的大小、位置和细胞形态，发展到稍微复杂的染色体得失计数。最近，基因表达谱为分子预测提供了一个高度准确和具有生物信息学意义的黄金标准。分子检测发展的最新一步是最近发现了主要驱动因素突变，这些突变允许对靶向分子疗法的反应进行预测测试。GNAQ和GNA11突变是促进细胞增殖的早期事件，这些突变对MAPK、PKC和AKT抑制剂敏感。BAP1、SF3B1和EIF1AX的突变是在很大程度上相互排斥的后期事件。BAP1基因突变与转移密切相关，而SF3B1和EIF1AX基因突变与预后良好相关。具有BAP1突变的葡萄膜黑色素瘤对表观遗传调节剂，如组蛋白脱乙酰酶抑制剂敏感。临床试验现在可以用来评估这些靶向分子制剂对葡萄膜黑色素瘤患者的疗效。分子预后检测和将高危患者纳入靶向分子治疗的临床试验正在迅速成为葡萄膜黑色素瘤治疗的标准护理。
To provide an update on the rapidly evolving methods for assessing prognosis and predicting response to targeted molecular therapy in uveal melanoma. The techniques for assessing prognosis in uveal melanoma have evolved from simple physical features, such as tumor size, location, and cell morphology, to the slightly more sophisticated counting of chromosomal gains and losses. More recently, gene expression profiling has provided a highly accurate and biologically informative gold standard for molecular prognostication. The latest step in the evolution of molecular testing has been the recent discovery of major driver mutations that allow predictive testing of response to targeted molecular therapies. Mutations in GNAQ and GNA11 are early events that promote cell proliferation, and these mutations are sensitive to MAPK kinase, PKC, and AKT inhibitors. Mutations in BAP1, SF3B1, and EIF1AX are later events that are largely mutually exclusive. Mutations in BAP1 are strongly associated with metastasis, whereas those in SF3B1 and EIF1AX are associated with good prognosis. Uveal melanomas with BAP1 mutations demonstrate sensitivity to epigenetic modulators, such as histone deacetylase inhibitors. Clinical trials are now available to evaluate the efficacy of these targeted molecular agents in patients with uveal melanoma. Molecular prognostic testing and enrollment of high-risk patients into clinical trials of targeted molecular therapy are rapidly becoming the standard of care in the management of uveal melanoma.