Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02215, USA.
Oncologist. 2013 Jun;18(6):717-25. doi: 10.1634/theoncologist.2012-0391. Epub 2013 May 24.
There have been significant advances in the treatment of malignant melanoma with the U.S. Food and Drug Administration approval of two drugs in 2011, the first drugs approved in 13 years. The developments of immune checkpoint modulation via cytotoxic T-lymphocyte antigen-4 blockade, with ipilimumab, and targeting of BRAF(V600), with vemurafenib or dabrafenib, as well as MEK, with trametinib, have been paradigm changing both for melanoma clinical practice and for oncology therapeutic development. These advancements, however, reveal new clinical questions regarding combinations and optimal sequencing of these agents in patients with BRAF mutant disease. We review the development of these agents, putative biomarkers, and resistance mechanisms relevant to their use, and possibilities for sequencing and combining these agents.
美国食品和药物管理局在 2011 年批准了两种药物，这是 13 年来首次批准的药物，这使得恶性黑色素瘤的治疗取得了重大进展。通过细胞毒性 T 淋巴细胞抗原-4 阻断的免疫检查点调节，以及针对 BRAF(V600)的药物，如 ipilimumab、vemurafenib 或 dabrafenib，以及 MEK 的 trametinib 的发展，不仅改变了黑色素瘤的临床实践，也改变了肿瘤治疗的发展模式。然而，这些进展揭示了新的临床问题，即这些药物在 BRAF 突变疾病患者中的联合应用和最佳应用顺序。我们回顾了这些药物的开发、相关的潜在生物标志物和耐药机制，以及这些药物的应用顺序和联合应用的可能性。
