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Drug resistance in targeted cancer therapies with RAF inhibitors 被引量:3
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作者 Ufuk Degirmenci Jiajun Yap +2 位作者 Yuen Rong MSim Shiru Qin Jiancheng Hu 《Cancer Drug Resistance》 2021年第3期665-683,共19页
Hyperactive RAS/RAF/MEK/ERK signaling has a well-defined role in cancer biology.Targeting this pathway results in complete or partial regression of most cancers.In recent years,cancer genomic studies have revealed tha... Hyperactive RAS/RAF/MEK/ERK signaling has a well-defined role in cancer biology.Targeting this pathway results in complete or partial regression of most cancers.In recent years,cancer genomic studies have revealed that genetic alterations that aberrantly activate the RAS/RAF/MEK/ERK signaling mainly occur on RAF or upstream,which motivated the extensive development of RAF inhibitors for cancer therapy.Currently,the first-generation RAF inhibitors have been approved for treating late-stage cancers with BRAF(V600E)mutations.Although these inhibitors have achieved promising outcomes in clinical treatments,their efficacy is abolished by quick-rising drug resistance.Moreover,cancers with hyperactive RAS exhibit intrinsic resistance to these drugs.To resolve these problems,the second-generation RAF inhibitors have been designed and are undergoing clinical evaluations.Here,we summarize the recent findings from mechanistic studies on RAF inhibitor resistance and discuss the critical issues in the development of next-generation RAF inhibitors with better therapeutic index,which may provide insights for improving targeted cancer therapy with RAF inhibitors. 展开更多
关键词 RAS/RAF/MEK/ERK signaling RAF/KSR family kinase oncogenic mutation targeted therapy RAF inhibitors drug resistance regulatory spine
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