Melanoma Institute Australia, University of Sydney, Sydney, Australia.
Ther Adv Med Oncol. 2013 Sep;5(5):278-85. doi: 10.1177/1758834013499637.
Until recently there was no effective systemic therapy for metastatic melanoma. Increased understanding of tumor biology and immune regulation has led to the development of drugs targeting the mitogen-activated protein kinase (MAPK) pathway (BRAF inhibitors and MEK inhibitors) and T-cell regulation (CTLA4 antibodies). These drugs are the new standard of care, however barriers to better patient outcomes include limited responses and significant toxicities (CTLA4 antibodies) and lack of durability in the majority of cases (BRAF and MEK inhibitors). This review discusses the next stages of development of treatments in melanoma, including immune checkpoint blocking drugs targeting the PD-1/PD-L1 axis, and the use of BRAF and MEK inhibitors in combination. Both approaches lead to a higher proportion of durable responses coupled with less toxicity. In an effort to improve outcomes even further, clinical trials of combinations of MAPK inhibitors, immunotherapies and other signal pathway inhibitors are underway. Adjuvant studies of many of these drugs have commenced, with the hope of also improving outcomes in patients with early-stage melanoma.
直到最近，转移性黑色素瘤还没有有效的系统治疗方法。对肿瘤生物学和免疫调节的深入了解导致了针对丝裂原活化蛋白激酶 (MAPK) 途径（BRAF 抑制剂和 MEK 抑制剂）和 T 细胞调节（CTLA4 抗体）的药物的发展。这些药物是新的标准治疗方法，然而，改善患者预后的障碍包括有限的反应和显著的毒性（CTLA4 抗体）以及大多数情况下缺乏持久性（BRAF 和 MEK 抑制剂）。本文讨论了黑色素瘤治疗的下一阶段的发展，包括针对 PD-1/PD-L1 轴的免疫检查点阻断药物，以及 BRAF 和 MEK 抑制剂的联合应用。这两种方法都导致更高比例的持久反应，同时毒性更小。为了进一步提高疗效，正在进行 MAPK 抑制剂、免疫疗法和其他信号通路抑制剂联合治疗的临床试验。这些药物中的许多药物的辅助研究已经开始，希望也能改善早期黑色素瘤患者的预后。
