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CRISPR Screens Identify Essential Cell Growth Mediators in BRAF Inhibitor-resistant Melanoma
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作者 Ziyi Li Binbin Wang +14 位作者 Shengqing Gu Peng Jiang Avinash Sahu Chen-Hao Chen Tong Han Sailing Shi Xiaoqing Wang Nicole Traugh Hailing Liu Yin Liu Qiu Wu Myles Brown Tengfei Xiao genevieve m.boland X.Shirley Liu 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2020年第1期26-40,共15页
BRAF is a serine/threonine kinase that harbors activating mutations in^7%of human malignancies and^60%of melanomas.Despite initial clinical responses to BRAF inhibitors,patients frequently develop drug resistance.To i... BRAF is a serine/threonine kinase that harbors activating mutations in^7%of human malignancies and^60%of melanomas.Despite initial clinical responses to BRAF inhibitors,patients frequently develop drug resistance.To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma,we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors.To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas,we integrate expression,ATAC-seq,and CRISPR screen data.We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6,which together enable resistance to BRAF inhibitors in melanoma cells.Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720,providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells. 展开更多
关键词 Drug resistance CRISPR screen MELANOMA BRAF inhibitor Gene regulation
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