Division of Medical Oncology, Department of Medicine and Surgery, Ospedale di Circolo e Fondazione Macchi, ASST dei Sette Laghi, 21100 Varese, Italy.
Unit of Medical Oncology, Department of Surgery and Medicine, University of Perugia, 06129 Perugia, Italy.
Int J Mol Sci. 2021 Dec 23;23(1):147. doi: 10.3390/ijms23010147.
Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to immunotherapy. Over the last years, whole-genome and exome sequencing techniques have led to increased knowledge on the molecular landscape of mucosal melanoma. Molecular studies have underlined noteworthy findings with potential therapeutic implications, including the presence of mutations, which are potential targets of tyrosine kinase inhibitors currently in use in the clinic (imatinib), but also mutation, amplifications, and gene deletions, which are presently under investigation in clinical trials. Recent results from a pooled analysis of patients with mucosal melanoma treated with immunotherapy have suggested that the combination of immune checkpoint inhibitors might improve survival outcomes in this subset of patients, as compared with single-agent immunotherapy. However, these results are not confirmed across different studies, and combo-immunotherapy correlates with a higher rate of adverse events. In this review, we describe the clinical, biological, and genetic features of mucosal melanoma. We also provide an update on the results of approved systemic treatment in this setting and overview the therapeutic strategies currently under investigation in clinical trials.
黏膜黑色素瘤是一种罕见且侵袭性较强的黑色素瘤亚型。与皮肤黑色素瘤不同，由于缺乏可操作的驱动突变和对免疫疗法的反应不佳，黏膜黑色素瘤仅从新的治疗方法中获得了有限的益处。近年来，全基因组和外显子组测序技术使人们对黏膜黑色素瘤的分子图谱有了更多的了解。分子研究强调了一些具有潜在治疗意义的显著发现，包括存在 突变，这些突变是目前临床上使用的酪氨酸激酶抑制剂（伊马替尼）的潜在靶点，以及 突变、 扩增和 基因缺失，这些目前正在临床试验中进行研究。最近对接受免疫治疗的黏膜黑色素瘤患者进行的一项汇总分析结果表明，与单药免疫治疗相比，免疫检查点抑制剂联合治疗可能改善这部分患者的生存结局。然而，这些结果在不同的研究中并未得到证实，并且联合免疫治疗与更高的不良事件发生率相关。在这篇综述中，我们描述了黏膜黑色素瘤的临床、生物学和遗传学特征。我们还提供了该治疗环境中已批准的系统治疗结果的最新信息，并概述了目前正在临床试验中研究的治疗策略。
