Cancer Center, The First Hospital of Jilin University, 1 Xinmin St, Changchun, 130021, China.
Curr Treat Options Oncol. 2022 Oct;23(10):1405-1427. doi: 10.1007/s11864-022-01007-6. Epub 2022 Sep 20.
Melanoma is one of the deadliest malignancies. Its incidence has been significantly increasing in most countries in recent decades. Acral melanoma (AM), a peculiar subgroup of melanoma occurring on the palms, soles, and nails, is the main subtype of melanoma in people of color and is extremely rare in Caucasians. Although great progress has been made in melanoma treatment in recent years, patients with AM have shown limited benefit from current therapies and thus consequently have worse overall survival rates. Achieving durable therapeutic responses in this high-risk melanoma subtype represents one of the greatest challenges in the field. The frequency of BRAF mutations in AM is much lower than that in cutaneous melanoma, which prevents most AM patients from receiving treatment with BRAF inhibitors. However, AM has more frequent mutations such as KIT and CDK4/6, so targeted therapy may still improve the survival of some AM patients in the future. AM may be less susceptible to immune checkpoint inhibitors because of the poor immunogenicity. Therefore, how to enhance the immune response to the tumor cells may be the key to the application of immune checkpoint inhibitors in advanced AM. Anti-angiogenic drugs, albumin paclitaxel, or interferons are thought to enhance the effectiveness of immune checkpoint inhibitors. Combination therapies based on the backbone of PD-1 are more likely to provide greater clinical benefits. Understanding the molecular landscapes and immune microenvironment of AM will help optimize our combinatory strategies.
黑色素瘤是最致命的恶性肿瘤之一。近几十年来，大多数国家的发病率都显著上升。肢端黑色素瘤（AM）是一种发生在手掌、脚底和指甲上的独特黑色素瘤亚组，是有色人种中黑色素瘤的主要亚型，在白种人中极为罕见。尽管近年来黑色素瘤的治疗取得了很大进展，但 AM 患者从当前治疗中获益有限，因此总体生存率较差。在这种高风险的黑色素瘤亚型中实现持久的治疗反应是该领域面临的最大挑战之一。AM 中 BRAF 突变的频率远低于皮肤黑色素瘤，这使得大多数 AM 患者无法接受 BRAF 抑制剂治疗。然而，AM 中更频繁出现 KIT 和 CDK4/6 等突变，因此靶向治疗可能仍能提高未来一些 AM 患者的生存率。由于免疫原性差，AM 可能对免疫检查点抑制剂的敏感性较低。因此，如何增强对肿瘤细胞的免疫反应可能是免疫检查点抑制剂在晚期 AM 中应用的关键。抗血管生成药物、白蛋白紫杉醇或干扰素被认为能增强免疫检查点抑制剂的疗效。以 PD-1 为基础的联合治疗更有可能提供更大的临床获益。了解 AM 的分子景观和免疫微环境将有助于优化我们的联合策略。
