Article
Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer.
Cancer cell - 12 Jan 2026
Zhang Yuetong, Chen Jiaying, She Yong, Fang Zhaoyuan, Zhang Yaxin, Ruan Danyun, Guo Wenjun, Liao Jianping, Zhou Weiping, Lao Jianpei, Fang Weicheng, Pan Xingyan, Kang Wenfei, Wang Zifeng, Wu Yuanzhong, Deng Rong, Tian Lin, Wang Liqin, Huang Huilin, Zheng Jian, Yan Yan, Lu Hezhe, Wang Ruiping, Yaeger Rona, Zhao Qi, Liao Wenting, Wang Feng, Gao Yijun
Abstract excerpt
While dual KRAS and epidermal growth factor receptor (EGFR) inhibition shows promise in treating KRAS-mutant colorectal cancer (CRC), resistance remains a major challenge. Using genetically engineered mouse models, patient-derived organoids and xenografts, as well as clinical specimens, we discover that colorectal tumors surviving combined KRAS and EGFR inhibition acquire a Paneth-like cell state-a secretory...
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