Fedorenko I V, Gibney G T, Sondak V K, Smalley K S M
The Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
The Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Br J Cancer. 2015 Jan 20;112(2):217-26. doi: 10.1038/bjc.2014.476. Epub 2014 Sep 2.
In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases—even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the future of combination strategies for patients with BRAF-mutant melanoma as well as the emerging therapeutic options for patients with NRAS-mutant and BRAF/NRAS-wild-type melanoma. We also outline some of the newest developments in the in-depth personalisation of therapy that should allow melanoma treatment to continue shaping the field precision cancer medicine.
近年来，黑色素瘤已成为癌基因导向的靶向治疗发展的典型代表。这种方法，以小分子BRAF抑制剂以及用于BRAF突变型黑色素瘤的BRAF/MEK抑制剂联合疗法的发展为例证，给患者带来了新的希望。尽管取得了这些成功，但在大多数情况下，治疗失败似乎几乎不可避免——即使是接受BRAF/MEK抑制剂双联疗法治疗的患者也是如此。在当前的综述中，我们讨论了BRAF突变型黑色素瘤患者联合治疗策略的未来，以及NRAS突变型和BRAF/NRAS野生型黑色素瘤患者新出现的治疗选择。我们还概述了治疗深度个体化方面的一些最新进展，这些进展应能使黑色素瘤治疗继续引领精准癌症医学领域的发展。
