A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAFV600E-Mutant Brain Tumor

BRAF 的二次突变导致 BRAFV600E 突变型脑肿瘤对 RAF 抑制产生耐药性

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作者：Jiawan Wang, Zhan Yao, Philip Jonsson, Amy N Allen, Alice Can Ran Qin, Sharmeen Uddin, Ira J Dunkel, Mary Petriccione, Katia Manova, Sofia Haque, Marc K Rosenblum, David J Pisapia, Neal Rosen, Barry S Taylor, Christine A Pratilas2
期刊：Cancer Discovery影响因子：29.700
时间：2018起止号：2018 Sep;8(9):1130-1141.
doi：10.1158/2159-8290.CD-17-1263研究方向： 肿瘤

Significance

In contrast to receptor tyrosine kinases, in which secondary mutations are often responsible for acquired resistance, second-site mutations in BRAF have not been validated in clinically acquired resistance to RAF inhibitors. We demonstrate a secondary mutation in BRAF (V600E/L514V) following progression on dabrafenib and confirm functionally that this mutation is responsible for resistance. Cancer Discov; 8(9); 1130-41. ©2018 AACR.See related commentary by Romano and Kwong, p. 1064This article is highlighted in the In This Issue feature, p. 1047.

Trial registration

ClinicalTrials.gov NCT01677741.

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