文章：

葡萄膜黑色素瘤治疗的新靶向和表观遗传治疗策略

New targeted and epigenetic therapeutic strategies for the treatment of uveal melanoma 

原文发布日期：2022-03-02 

英文摘要：

Uveal melanoma (UM) is a rare, genetically bland ocular malignancy with excellent local treatment options, but no disease-specific therapies are approved for use in the metastatic setting by the Food and Drug Administration. Metastatic UM (mUM) confers a prognosis of ~15 months. Unlike cutaneous melanoma, UM is poorly responsive to checkpoint inhibitors and cytotoxic chemotherapy highlighting the importance of clarifying vulnerable disease-specific mechanisms, such as cell cycle or metabolic pathways necessary for tumor growth and survival. The elucidation of signaling pathways downstream of the frequently mutated GNA GTPase such as PKC/MAPK/ERK/MEK, PI3K/AKT, and YAP-Hippo have offered potential targets. Potentially druggable epigenetic targets due to BAP1-mutated UM have also been identified, including proteins involved with histone deacetylation and DNA splicing. This review describes the preclinical rationale for the development of targeted therapies and current strategies currently being studied in clinical trials or will be in the near future. 

摘要翻译： 

葡萄膜黑色素瘤（UM）是一种罕见、遗传背景单一的 ocular malignancy（眼部恶性肿瘤），虽具有优异的局部治疗方案，但美国食品药品监督管理局尚未批准任何针对转移性疾病的特异性疗法。转移性葡萄膜黑色素瘤（mUM）的预后约为15个月。与皮肤黑色素瘤不同，UM对检查点抑制剂和细胞毒性化疗反应较差，这凸显了阐明疾病特异性脆弱机制的重要性，例如肿瘤生长和生存所必需的细胞周期或代谢通路。对频繁突变的GNA GTPase下游信号通路（如PKC/MAPK/ERK/MEK、PI3K/AKT和YAP-Hippo）的阐释提供了潜在治疗靶点。BAP1突变型UM也带来了潜在的表观遗传学药物靶点，包括组蛋白去乙酰化和DNA剪接相关蛋白。本综述阐述了靶向治疗开发的临床前理论基础，以及当前正在临床试验中或近期即将开展研究的策略。

原文链接：

New targeted and epigenetic therapeutic strategies for the treatment of uveal melanoma