期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/ijms22189890
关键词
BRAF; MEK; targeted therapy; immunological effects; immune checkpoint inhibitors; metastatic melanoma; CTLA-4; PD-1; PD-L1; paradoxical ERK activation; inflammasome; tumor microenvironment
资金
- Deutsche Forschungsgemeinschaft [SFB1066]
- Else Kroner Fresenius Foundation
- University Medical Center Mainz
The advent of MAPK inhibitors and ICI has greatly improved the treatment of metastatic melanoma, with BRAF/MEK inhibitors used for BRAF mutation patients, showing immunomodulatory functions in addition to their antiproliferative effects.
The advent of mitogen-activated protein kinase (MAPK) inhibitors that directly inhibit tumor growth and of immune checkpoint inhibitors (ICI) that boost effector T cell responses have strongly improved the treatment of metastatic melanoma. In about half of all melanoma patients, tumor growth is driven by gain-of-function mutations of BRAF (v-rat fibrosarcoma (Raf) murine sarcoma viral oncogene homolog B), which results in constitutive ERK activation. Patients with a BRAF mutation are regularly treated with a combination of BRAF and MEK (MAPK/ERK kinase) inhibitors. Next to the antiproliferative effects of BRAF/MEKi, accumulating preclinical evidence suggests that BRAF/MEKi exert immunomodulatory functions such as paradoxical ERK activation as well as additional effects in non-tumor cells. In this review, we present the current knowledge on the immunomodulatory functions of BRAF/MEKi as well as the non-intended effects of ICI and discuss the potential synergistic effects of ICI and MAPK inhibitors in melanoma treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据