Flaherty Keith T
Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
Pigment Cell Melanoma Res. 2023 Nov;36(6):563-575. doi: 10.1111/pcmr.13125. Epub 2023 Sep 28.
Melanoma had long been considered to be particularly addressable with immunotherapy, but that reputation was built on modestly effective cytokine-based immunotherapy. CTLA-4 antibody therapy reinforced this legacy, but PD-1 antibodies transformed the melanoma treatment landscape and lead the way for immunotherapy to become standard treatment for more than half of the advanced cancer population. BRAF mutations were discovered in 8% of all cancer and nearly 50% of melanomas. Successful development of BRAF inhibitors and BRAF/MEK combination therapy in melanoma preceded regulatory approval across all cancer types. No cancer type saw outcomes improved by the same margin as melanoma in the decade of the 2010s.
长期以来,黑色素瘤一直被认为特别适合采用免疫疗法进行治疗,但其这一声誉建立在基于细胞因子的疗效一般的免疫疗法之上。CTLA-4抗体疗法巩固了这一传统疗法,但PD-1抗体改变了黑色素瘤的治疗格局,并引领免疫疗法成为半数以上晚期癌症患者的标准治疗方法。在所有癌症中,8%的患者以及近50%的黑色素瘤患者存在BRAF突变。在黑色素瘤中成功研发出BRAF抑制剂和BRAF/MEK联合疗法之后,才在所有癌症类型中获得监管批准。在2010年代的十年间,没有哪种癌症类型的治疗效果能像黑色素瘤那样得到如此大幅的改善。