葡萄膜黑色素瘤 (UM) 是一种孤儿癌，尽管它是成人中最常见的眼部肿瘤。尽管与皮肤黑色素瘤存在显着的遗传、生物学和临床差异，但患者经常到皮肤癌中心接受转移性疾病的治疗。转移性 UM 最常用的治疗方法是 tebentafusp 和联合免疫检查点阻断，这两种方法的缓解率较低，并且可能伴随着高昂的治疗成本和显着的免疫相关毒性。因此，识别预测治疗反应的生物标志物和临床特征并寻找新的治疗靶点至关重要。在一组回顾性研究中，免疫检查点阻断的使用在肝外疾病和血清乳酸脱氢酶水平正常的患者中显示出更有利的结果，使其在该亚组中的使用更加合理。为了确定新的药物靶点，我们将使用下一代纳米孔测序分析患者生物样本中神经嵴转录因子的表达和相关性。计算机算法和基于网络的分析将有助于识别可药物靶标，这些靶标随后将在源自患者的短期细胞培养物中得到验证。这种方法将有助于为 UM 找到新颖且个性化的治疗方法。© 2023 作者。约翰·威利 (John Wiley) 出版的《德国皮肤科杂志》

Uveal melanoma (UM) is an orphan cancer despite being the most common eye tumor in adults. Patients often present to skin cancer centers for treatment of metastatic disease although there are significant genetic, biological, and clinical differences from cutaneous melanoma. The treatments most commonly used for metastatic UM are tebentafusp and combined immune checkpoint blockade, both of which yield low response rates and may be accompanied by high treatment costs and significant immune-related toxicities. Thus, it is of paramount importance to identify biomarkers and clinical profiles predictive of treatment response and to find novel therapeutic targets. The use of immune checkpoint blockade showed more favorable outcomes in patients with extrahepatic disease and normal levels of serum lactate dehydrogenase in a panel of retrospective studies, making its use more reasonable in this subgroup. To identify novel drug targets, we will analyze the expression and relevance of neural crest transcription factors in patient bio-specimens using next-generation nanopore sequencing. Computer algorithms and network-based analysis will facilitate the identification of druggable targets which will subsequently be validated in patient-derived short-term cell cultures. This approach will help to find novel and personalized treatments for UM.© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.