期刊
PHARMACEUTICS
卷 13, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13091427
关键词
neuroblastoma; anaplastic lymphoma kinase; point mutations; monotherapy; combinatory therapy; drug resistance
资金
- Norwegian Childhood Cancer Society [190004, 180007]
Neuroblastoma is a malignant tumor that mostly affects young children and is highly heterogeneous, with risk factors including abnormalities in the ALK gene leading to tumorigenesis. Combination therapy with ALK inhibitors may be an effective strategy to reduce drug resistance and improve treatment outcomes.
Neuroblastoma (NBL) is an embryonic malignancy of the sympathetic nervous system and mostly affects children under the age of five. NBL is highly heterogeneous and ranges from spontaneously regressing to highly aggressive disease. One of the risk factors for poor prognosis are aberrations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), which is involved in the normal development and function of the nervous system. ALK mutations lead to constitutive activation of ALK and its downstream signalling pathways, thus driving tumorigenesis. A wide range of steric ALK inhibitors has been synthesized, and several of these inhibitors are already in clinical use. Major challenges are acquired drug resistance to steric inhibitors and pathway evasion strategies of cancer cells upon targeted therapy. This review will give a comprehensive overview on ALK inhibitors in clinical use in high-risk NBL and on the potential and limitations of novel inhibitors. Because combinatory treatment regimens are probably less likely to induce drug resistance, a special focus will be on the combination of ALK inhibitors with drugs that either target downstream signalling pathways or that affect the survival and proliferation of cancer cells in general.
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