Article
Mevalonate pathway rewiring driven by enhancer remodelling confers resistance to KRAS inhibitors in colorectal cancer.
Nature communications - 2 Jun 2026
Guo Yaoyu, Zhong Yi, Hu Peishan, Chen Yufeng, Guo Wenjun, Chen Jianfeng, Guan Peiyong, Zhou Zhengran, Zhu Fang, Zeng Xian, Gao Jiuping, Xiong Qiqing, Yu Zhaoliang, Hu Chuling, Cai Zerong, Xie Xiaoyu, Hong Jing Han, Chan Jason Yongsheng, Wang Wenyu, Diao Dechang, Xia Xiaojun, Yu Qiang, Ong Choon Kiat, Gao Yijun, Wu Xiaojian, Tan Jing
Abstract excerpt
KRAS inhibitors (KRASi) have emerged as promising new cancer therapeutics for KRAS-mutant cancers; however, resistance remains a potential clinical challenge. Here, we show that reactivation of ERK is a hallmark of KRASi-resistant colorectal cancers (CRCs) and further demonstrate that enhancer remodeling rewires cholesterol biosynthesis through the mevalonate (MVA) pathway to confer this resistance....
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