The biology of uveal melanoma.
The biology of uveal melanoma.
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DOI：
10.1007/s10555-017-9663-3
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Pfeffer U
中科院分区：
文献类型：
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作者：
Amaro A;Gangemi R;Piaggio F;Angelini G;Barisione G;Ferrini S;Pfeffer U
葡萄膜黑色素瘤（UM）是一种罕见的眼部癌症，其病因、突变频率和特征以及对靶向治疗和免疫检查点阻滞剂的耐药性等临床行为与皮肤黑色素瘤不同。原发疾病可以通过手术或放射治疗有效地控制，但大约一半的UMs发生远处转移，主要转移到肝脏。转移患者的生存期低于1年，几十年来没有改善。近年来，人们对以G蛋白GNAQ和GNA11启动突变为特征的UM生物学有了深入的了解。细胞遗传学改变，特别是3号染色体的单体和8号染色体长臂的扩增，以及brca1相关蛋白1、BAP1（一种肿瘤抑制基因）或剪接因子SF3B1的突变决定了UM的转移。细胞遗传学和分子分析允许一个非常精确的预测，仍然不匹配有效的辅助治疗。G蛋白信号已被证明可以独立于HIPPO激活YAP/TAZ通路，而通过丝裂原激活的激酶通路的传统信号也可能有助于UM的发展和进展。多项证据表明，炎症和巨噬细胞在UM及其肝转移中起促瘤作用。UM细胞受益于眼睛的免疫特权，并可能采用几种机制参与这种特权，即使在离开生态位后也能使肿瘤逃逸。在这里，我们回顾了目前对UM生物学的了解，并讨论了UM治疗的最新方法。
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.