A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-like Cells

著者: Ilana Chefetz, Edward Grimley, Kun Yang, Linda Hong, Ekaterina V. Vinogradova, Radu M. Suciu, Ilya Kovalenko, David Karnak, Cynthia A. Morgan, Mikhail Chtcherbinine, Cameron D. Buchman, Brandt C. Huddle, Scott J. Barraza, Meredith A. Morgan, Kara A. Bernstein, Euisik Yoon, David B. Lombard, Andrea H. Bild, Geeta Mehta, Iris L. Romero, Chun-Yi Chiang, Charles N. Landen, Benjamin F. Cravatt, Thomas D. Hurley, Scott D. Larsen, Ronald J. Buckanovich - Cell Reports 2019 被引用: 146

ovarian cancer stem-like cells (CSCs). ALDH1Ai induce necroptotic CSC death, mediated, in part, by the induction of mitochondrial uncoupling proteins and reduction in oxidative phosphorylation. ALDH1Ai is highly synergistic with chemotherapy, reducing tumor initiation capacity and increasing tumor eradication in vivo. These studies link ALDH1A with necroptosis and confirm the family as a critical therapeutic target to overcome chemotherapy resistance and improve patient outcomes.