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

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 1 2021

Keywords

  • CDK inhibitor
  • Dinaciclib
  • Endometrial cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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