Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Antitumor T-cell Immunity

通过将 MEK 从 ERK 中隔离并促进抗肿瘤 T 细胞免疫来持久抑制癌症中获得性 MEK 抑制剂耐药性

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作者:Aayoung Hong #, Marco Piva #, Sixue Liu #, Willy Hugo, Shirley H Lomeli, Vincent Zoete, Christopher E Randolph, Zhentao Yang, Yan Wang, Jordan J Lee, Skylar J Lo, Lu Sun, Agustin Vega-Crespo, Alejandro J Garcia, David B Shackelford, Steven M Dubinett, Philip O Scumpia, Stephanie D Byrum, Alan J Tack

Significance

Type I RAFi + MEKi are indicated only in certain BRAF V600MUT cancers. In contrast, type II RAFi + MEKi are durably active against acquired MEKi resistance across broad cancer indications, which reveals exquisite MAPK addiction. Allosteric modulation of MAPK protein/protein interactions and temporal preservation of intratumoral CD8+ T cells are mechanisms that may be further exploited.This article is highlighted in the In This Issue feature, p. 521.

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