Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA, USA.
J Pathol. 2014 Jan;232(2):134-41. doi: 10.1002/path.4259.
Over the past 30 years, and despite extensive clinical research, the treatment options for metastatic melanoma have been limited. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimes have failed to show significant improvement in overall survival. Recent advances and in-depth understanding of the biology of melanoma have contributed in the development of new agents and to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. Since the discovery of activating mutations in the BRAF oncogene, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma, with unprecedentedly high response rates. Inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided clinically validated targets for cancer immunotherapy, resulting in durable tumour responses. The combination of both approaches may result in additional benefits. Here we discuss current molecular targeted treatment options, immunotherapy and promising ongoing research to develop new strategies to treat melanoma.
在过去的 30 年中，尽管进行了广泛的临床研究，但转移性黑色素瘤的治疗选择仍然有限。单药和联合化疗、激素治疗、生物化疗、免疫治疗、靶向药物治疗和联合治疗方案均未能显示出总生存期的显著改善。近年来，对黑色素瘤生物学的深入了解促进了新药物的开发，并改变了黑色素瘤作为最具耐药性恶性肿瘤之一的观念。自发现 BRAF 癌基因的激活突变以来，针对不可切除和转移性黑色素瘤的靶向治疗取得了显著进展，反应率空前高。免疫调节检查点的失活限制了 T 细胞对黑色素瘤的反应，为癌症免疫治疗提供了临床验证的靶点，导致肿瘤持久缓解。这两种方法的结合可能会带来额外的益处。本文讨论了目前的分子靶向治疗选择、免疫治疗以及正在进行的有前途的研究，以开发治疗黑色素瘤的新策略。
