Antitumor effects of a covalent cyclin-dependent kinase 7 inhibitor in colorectal cancer. Issue 5 (June 2019)

• Record Type: Journal Article
• Authors: Wang, Jian; Li, Zhenyu; Mei, Hong; Zhang, Dejun; Wu, Gang; Zhang, Tao; Lin, Zhenyu
• Is Part Of: Anti-cancer drugs. Volume 30:Issue 5(2019)
• Publication Date: 2019-06
• Subjects: CDK7 -- colorectal cancer -- Myc -- transcription; Antineoplastic agents -- Periodicals; Cancer -- Chemotherapy -- Periodicals; Antineoplastic Agents -- therapeutic use -- Periodicals; Drug Therapy -- Periodicals; 616.994061
• DOI: 10.1097/CAD.0000000000000749
• Languages: English
• ISSNs: 0959-4973

Abstract

Abstract : Although both antiepidermal growth factor receptor and vascular endothelial growth factor therapies have been shown to be effective against colorectal cancer (CRC), their beneficial effects are limited to a small proportion of patients and are not sustainable. Cyclin-dependent kinase 7 (CDK7) is an important regulator of the transcriptional machinery. Use of small-molecule inhibitors of the transcriptional machinery has shown promising selectivity for cancer cells and potent antiproliferative effects. In this study, the effects of a covalent CDK7 inhibitor THZ1 as a potent anti-CRC compound were evaluated in vitro and in vivo . THZ1 significantly inhibited cell growth and induced apoptosis of CRC cells in vitro . In addition, it also decreased xenograft tumor growth in vivo . RNA-Seq showed that THZ1 induced inhibition of a number of oncogenic transcripts. Taken together, our results indicate that pharmacological modulation of CDK7 kinase activity by THZ1 may represent a potential strategy in the treatment of CRC. Abstract : Supplemental Digital Content is available in the text.