Article
Targeting WEE1 in ARID1A/TP53 Concurrent Mutant Colorectal Cancer by Exploiting R-Loop Accumulation and DNA Repair Deficiencies.
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 1 Feb 2026
Zhang Chi, Zhu Yanjing, Ai Luoyan, Wang Jingyuan, Yu Shan, Wang Yichen, Xu Xiaojing, Liu Mengling, Yu Yiyi, Zhu Mengxuan, Liu Yutong, Xu Zhenghang, Zhou Haojie, Li Huishan, Huang Qihong, Liu Qing, Peng Ke, Liu Tianshu
Abstract excerpt
ARID1A, a component of the SWI/SNF tumor suppressor complex, is frequently mutated in colorectal cancers (CRC). Here, it is found that CRC with ARID1A/TP53 concurrent mutations is highly sensitive to WEE1 inhibitors. ARID1A deficiency promoted the accumulation of R-loops, leading to replication stress. This stress, combined with the loss of G1/S and G2/M checkpoint controls due to P53 and WEE1 dysfunction,...
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