Article
RAF dimer inhibition enhances the antitumor activity of MEK inhibitors in K-RAS mutant tumors.
Molecular oncology - 1 Aug 2020
Yuan Xi, Tang Zhiyu, Du Rong, Yao Zhan, Cheung Shing-Hu, Zhang Xinwen, Wei Jing, Zhao Yuan, Du Yunguang, Liu Ye, Hu Xiaoxia, Gong Wenfeng, Liu Yong, Gao Yajuan, Huang Zhiyue, Cao Zongfu, Wei Min, Zhou Changyou, Wang Lai, Rosen Neal, Smith Paul D, Luo Lusong
Abstract excerpt
The mutation of K-RAS represents one of the most frequent genetic alterations in cancer. Targeting of downstream effectors of RAS, including of MEK and ERK, has limited clinical success in cancer patients with K-RAS mutations. The reduced sensitivity of K-RAS-mutated cells to certain MEK inhibitors (MEKi) is associated with the feedback phosphorylation of MEK by C-RAF and with the reactivation of...
Topics
- Allosteric Regulation
- Animals
- Antineoplastic Agents
- Benzimidazoles
- Cell Line, Tumor
- Cell Proliferation
- Humans
- Mice
- Mitogen-Activated Protein Kinase Kinases
- Mutation