Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany.
Department of Surgical Oncology, Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, Netherlands.
Lancet. 2018 Sep 15;392(10151):971-984. doi: 10.1016/S0140-6736(18)31559-9.
Cutaneous melanoma causes 55 500 deaths annually. The incidence and mortality rates of the disease differ widely across the globe depending on access to early detection and primary care. Once melanoma has spread, this type of cancer rapidly becomes life-threatening. For more than 40 years, few treatment options were available, and clinical trials during that time were all unsuccessful. Over the past 10 years, increased biological understanding and access to innovative therapeutic substances have transformed advanced melanoma into a new oncological model for treating solid cancers. Treatments that target B-Raf proto-oncogene serine/threonine-kinase (BRAF) (Val600) mutations using selected BRAF inhibitors combined with mitogen-activated protein kinase inhibitors have significantly improved response and overall survival. Furthermore, advanced cutaneous melanoma has developed into a prototype for testing checkpoint-modulating agents, which has increased hope for long-term tumour containment and a potential cure. These expectations have been sustained by clinical success with targeted agents and antibodies that block programmed cell-death protein 1 in locoregional disease, which induces prolongation of relapse-free, distant-metastasis-free, and overall survival times.
皮肤黑色素瘤每年导致 55500 人死亡。由于早期发现和初级保健的机会不同,该疾病的发病率和死亡率在全球范围内差异很大。一旦黑色素瘤扩散,这种癌症就会迅速危及生命。40 多年来,治疗选择非常有限,而当时的临床试验均未成功。在过去的 10 年中,由于对生物学的深入了解以及能够获得创新的治疗物质,晚期黑色素瘤已成为治疗实体瘤的新肿瘤模型。使用选择性 BRAF 抑制剂联合丝裂原活化蛋白激酶抑制剂治疗针对 B-Raf 原癌基因丝氨酸/苏氨酸激酶(BRAF)(Val600)突变的治疗方法显著提高了反应率和总生存率。此外,晚期皮肤黑色素瘤已成为检测检查点调节药物的原型,这增加了长期肿瘤控制和潜在治愈的希望。靶向药物和抗体在局部疾病中阻断程序性细胞死亡蛋白 1 的临床成功维持了这些期望,这些药物延长了无复发生存期、无远处转移生存期和总生存期。