Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Center for Melanoma, Harvard Medical School, Boston, Massachusetts.
Clin Cancer Res. 2019 Oct 1;25(19):5735-5742. doi: 10.1158/1078-0432.CCR-18-0836. Epub 2019 Apr 16.
The characterization of the MAPK signaling pathway has led to the development of multiple promising targeted therapy options for a subset of patients with metastatic melanoma. The combination of BRAF and MEK inhibitors represents an FDA-approved standard of care in patients with metastatic and resected BRAF-mutated melanoma. There are currently three FDA-approved BRAF/MEK inhibitor combinations for the treatment of patients with BRAF-mutated melanoma. Although there have been significant advances in the field of targeted therapy, further exploration of new targets within the MAPK pathway will strengthen therapeutic options for patients. Important clinical and translational research focuses on mechanisms of resistance, predictive biomarkers, and challenging patient populations such as those with brain metastases or resected melanoma.
MAPK 信号通路的特征描述导致了针对转移性黑色素瘤亚组患者的多种有前途的靶向治疗选择的发展。BRAF 和 MEK 抑制剂的联合治疗代表了转移性和可切除 BRAF 突变黑色素瘤患者的 FDA 批准的标准治疗方法。目前有三种 FDA 批准的 BRAF/MEK 抑制剂联合治疗方案用于治疗 BRAF 突变黑色素瘤患者。尽管在靶向治疗领域取得了重大进展,但对 MAPK 通路内新靶点的进一步探索将为患者提供更多的治疗选择。重要的临床和转化研究侧重于耐药机制、预测生物标志物以及具有挑战性的患者群体,如脑转移或切除的黑色素瘤患者。