Chang-Ching Lin, Tsung-Cheng Chang, Yunguan Wang, Lei Guo, Yunpeng Gao, Emmanuel Bikorimana, Andrew Lemoff, Yisheng V Fang, He Zhang, Yanfeng Zhang, Dan Ye, Isabel Soria-Bretones, Alberto Servetto, Kyung-Min Lee, Xuemei Luo, Joseph J Otto, Hiroaki Akamatsu, Fabiana Napolitano, Ram Mani, David W Cescon, Lin Xu, Yang Xie, Joshua T Mendell, Ariella B Hanker, Carlos L Arteaga
CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells...
March 13, 2024: Nature Communications