作者: Kang Dai , Cong Li , Lingming Liang , Minqing Rong , Jessica Orf
DOI: 10.1158/1538-7445.AM2012-LB-249
关键词:
摘要: Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL CDK4 and CDK6 are two highly related cyclin D-dependent cell cycle regulatory kinases. CDK4/6 activity promotes G1 to S phase transition by phosphorylating the retinoblastoma (Rb) tumor suppressor protein. Here, we report characterization of a potent, selective orally-available small molecule inhibitor for treating Rb-positive cancer. The was over 1000-fold more potent in inhibiting CDK4 than CDK1. It also showed Rb-dependent anti-proliferative both cancer lines xenograft models. A greater degree variation sensitivity observed colon compared other tested. To understand this difference sensitivity, isolated inhibitor-resistant cells growing sensitive presence inhibitor. Gene expression parental resistant analyzed compared. Cyclin E1, CDK2 cyclin, found be most significantly overexpressed gene cells. Consistent with this, CDK2-associated E1 protein kinase were increased These results suggest that high may make tumors less inhibition could potential marker patient selection treatment inhibitor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings American Association Cancer Research; 2012 31-Apr 4; IL. Philadelphia (PA): AACR; Res 2012;72(8 Suppl):Abstract nr LB-249. doi:1538-7445.AM2012-LB-249