When CDK4/6i meets GPX4i: Stop dividing to die iron hard

In this issue of Cell Chemical Biology, Rodencal et al. 1 Rodencal J. Kim N. He A. Li V.L. Lange M. He J. Tarangelo A. Schafer Z.T. Olzmann J.A. Long J.Z. et al. Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest. Cell Chem. Biol. 2023; 31: 234-248https://doi.org/10.1016/j.chembiol.2023.10.011 Abstract Full Text Full Text PDF Scopus (0) Google Scholar report that cell-cycle arrest by p53 stabilizers or CDK4/6 inhibitors (CDK4/6i) can lead to phospholipid remodeling and hence sensitize cancer cells to GPX4 inhibitor (GPX4i)-triggered ferroptosis. This study suggests a novel cancer therapeutic strategy combining CDK4/6i with GPX4i. In this issue of Cell Chemical Biology, Rodencal et al. 1 Rodencal J. Kim N. He A. Li V.L. Lange M. He J. Tarangelo A. Schafer Z.T. Olzmann J.A. Long J.Z. et al. Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest. Cell Chem. Biol. 2023; 31: 234-248https://doi.org/10.1016/j.chembiol.2023.10.011 Abstract Full Text Full Text PDF Scopus (0) Google Scholar report that cell-cycle arrest by p53 stabilizers or CDK4/6 inhibitors (CDK4/6i) can lead to phospholipid remodeling and hence sensitize cancer cells to GPX4 inhibitor (GPX4i)-triggered ferroptosis. This study suggests a novel cancer therapeutic strategy combining CDK4/6i with GPX4i. Sensitization of cancer cells to ferroptosis coincident with cell cycle arrestRodencal et al.Cell Chemical BiologyNovember 13, 2023In BriefFerroptosis regulation remains poorly understood. Rodencal et al. demonstrate that cell cycle arrest enhances sensitivity to ferroptosis when ferroptosis is induced by direct inhibition of GPX4. It may be possible to target this mechanism in vivo using growth-arresting agents together with an orally bioavailable GPX4 inhibitor. Full-Text PDF