Dinaciclib, a bimodal agent effective against endometrial cancer

David Howard, David James, Kate Murphy, Jezabel Garcia-Parra, Belen Pan-Castillo, Stuart Rex, Annemarie Moul, Eilir Jones, Marc Bilbao-Asensio, Saul Michue-Seijas, Kerryn Lutchman-Singh, Lavinia Margarit, Lewis W. Francis, Paul Rees, Deyarina Gonzalez, R. Steven Conlan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Endometrial cancer (EC) is the sixth most prevalent female cancer globally and although high rates of success are achieved when diagnosed at an early stage, the 5-year survival rate for cancers diagnosed at Stages II–IV is below 50%. Improving patient outcomes will necessitate the introduction of novel therapies to the clinic. Pan-cyclin-dependent kinase inhibitors (CDKis) have been explored as therapies for a range of cancers due to their ability to simultaneously target multiple key cellular processes, such as cell cycle progression, transcription, and DNA repair. Few stud-ies, however, have reported on their potential for the treatment of EC. Herein, we examined the effects of the pan-CDKi dinaciclib in primary cells isolated directly from tumors and EC cell lines. Dinaciclib was shown to elicit a bimodal action in EC cell lines, disrupting both cell cycle progression and phosphorylation of the RNA polymerase carboxy terminal domain, with a concomitant reduction in Bcl-2 expression. Furthermore, the therapeutic potential of combining dinaciclib and cisplatin was explored, with the drugs demonstrating synergy at specific doses in Type I and Type II EC cell lines. Together, these results highlight the potential of dinaciclib for use as an effective EC therapy.

Original languageEnglish (US)
Article number1135
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume13
Issue number5
DOIs
StatePublished - Mar 6 2021

Keywords

  • CDK inhibitor
  • Dinaciclib
  • Endometrial cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Dinaciclib, a bimodal agent effective against endometrial cancer'. Together they form a unique fingerprint.

Cite this