University of Pittsburgh, Medicine, 200 Lothrop Street, Pittsburgh 15213, PA, USA.
Expert Opin Investig Drugs. 2012 Nov;21(11):1643-59. doi: 10.1517/13543784.2012.713938. Epub 2012 Aug 9.
Therapies targeting immune checkpoints (CTLA-4) and the MAP kinase signaling pathway (RAS/RAF/MEK/ERK) have transformed the treatment of advanced melanoma in the past year. Agents aimed at other therapeutic targets of interest are being actively evaluated in the clinic.
Areas of active therapeutic interest in melanoma include immunotherapy, molecularly targeted therapy and chemotherapy; combinations of these modalities are now under systematic exploration.
The evaluation of patients with melanoma now includes the molecular profiling of tumor mutations in the BRAF, as well as c-Kit, NRAS and other genes that have been discovered to be drivers of different subsets of the disease. The analysis of the host immunological response to melanoma is equally important, as a basis for the development of immunotherapies that have been of value to melanoma patients in the adjuvant arena, as well as for therapy of metastatic disease. The understanding of these two facets of the disease will provide a more rational basis for the delivery of individualized therapy for the disease both in its advanced setting, and in the adjuvant arena, in the future.
在过去一年中,针对免疫检查点(CTLA-4)和 MAP 激酶信号通路(RAS/RAF/MEK/ERK)的治疗方法改变了晚期黑色素瘤的治疗格局。目前正在临床积极评估针对其他治疗靶点的药物。
黑色素瘤的治疗靶点包括免疫治疗、分子靶向治疗和化疗;这些方法的联合应用正在系统探索中。
目前对黑色素瘤患者的评估包括对 BRAF 以及 c-Kit、NRAS 和其他基因的肿瘤突变进行分子谱分析,这些基因已被发现是疾病不同亚群的驱动基因。对宿主对黑色素瘤免疫反应的分析同样重要,因为它为开发免疫疗法提供了基础,这些免疫疗法在辅助治疗领域以及转移性疾病的治疗中对黑色素瘤患者具有价值。对这两个疾病方面的了解将为未来晚期疾病和辅助治疗领域的个体化治疗提供更合理的依据。