Jing Li, Thomas A Hilimire, Liu Yueying, Lili Wang, Jiaxin Liang, Balázs Győrffy, Vitali Sikirzhytski, Hao Ji, Li Zhang, Chen Cheng, Xiaokai Ding, Kendall R Kerr, Charles E Dowling, Alexander A Chumanevich, Zachary T Mack, Gary P Schools, Chang-Uk Lim, Leigh Ellis, Xiaolin Zi, Donald C Porter, Eugenia V Broude, Campbell McInnes, George Wilding, Michael B Lilly, Igor B Roninson, Mengqian Chen
Mediator kinases CDK19 and CDK8, pleiotropic regulators of transcriptional reprogramming, are differentially regulated by androgen signaling but both kinases are upregulated in castration-resistant prostate cancer (CRPC). Genetic or pharmacological inhibition of CDK8 and CDK19 reverses the castration-resistant phenotype and restores the sensitivity of CRPC xenografts to androgen deprivation in vivo. Prolonged CDK8/19 inhibitor treatment combined with castration not only suppresses the growth of CRPC xenografts but also induces tumor regression and cures...
March 28, 2024: Journal of Clinical Investigation