Advanced cutaneous melanoma is considered to be the most aggressive type of skin cancer and has variable rates of treatment response. Currently, there are some classes of immunotherapy and target therapies for its treatment. Immunotherapy can inhibit tumor growth and its recurrence by triggering the host’s immune system, whereas targeted therapy inhibits specific molecules or signaling pathways. However, melanoma responses to these treatments are highly heterogeneous, and patients can develop resistance. Epigenomics (DNA/histone modifications) contribute to cancer initiation and progression. Epigenetic alterations are divided into four levels of gene expression regulation: DNA methylation, histone modification, chromatin remodeling, and non-coding RNA regulation. Deregulation of lysine methyltransferase enzymes is associated with tumor initiation, invasion, development of metastases, changes in the immune microenvironment, and drug resistance. The study of lysine histone methyltransferase (KMT) and nicotinamide N-methyltransferase (NNMT) inhibitors is important for understanding cancer epigenetic mechanisms and biological processes. In addition to immunotherapy and target therapy, the research and development of KMT and NNMT inhibitors is ongoing. Many studies are exploring the therapeutic implications and possible side effects of these compounds, in addition to their adjuvant potential to the approved current therapies. Importantly, as with any drug development, safety, efficacy, and specificity are crucial considerations when developing methyltransferase inhibitors for clinical applications. Thus, this review article presents the recently available therapies and those in development for advanced cutaneous melanoma therapy.
晚期皮肤黑色素瘤被认为是最具侵袭性的皮肤癌类型，其治疗反应率存在显著差异。目前临床上主要采用免疫疗法和靶向疗法进行治疗。免疫疗法通过激活宿主免疫系统抑制肿瘤生长及复发，而靶向疗法则通过抑制特定分子或信号通路发挥作用。然而黑色素瘤对这些治疗的反应具有高度异质性，且患者易产生耐药性。表观基因组学（DNA/组蛋白修饰）在癌症发生发展中起关键作用，其调控机制可分为四个层面：DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA调控。赖氨酸甲基转移酶功能失调与肿瘤发生、侵袭转移、免疫微环境改变及耐药性发展密切相关。对组蛋白赖氨酸甲基转移酶（KMT）和烟酰胺N-甲基转移酶（NNMT）抑制剂的研究，对于理解癌症表观遗传机制及生物学进程具有重要意义。除现有免疫疗法和靶向疗法外，KMT与NNMT抑制剂的研发正在持续推进。众多研究不仅探索这些化合物的治疗潜力及潜在副作用，同时评估其作为现有标准疗法辅助治疗的协同效应。值得注意的是，与所有药物研发相同，甲基转移酶抑制剂的临床应用必须重点考量其安全性、有效性和特异性。本综述系统阐述了晚期皮肤黑色素瘤现有疗法及处于研发阶段的新型治疗策略。
肿瘤(癌症)患者之家