Targeting CDK4 (cyclin-dependent kinase) amplification in liposarcoma: A comprehensive review

Crit Rev Oncol Hematol. 2020 Sep:153:103029. doi: 10.1016/j.critrevonc.2020.103029. Epub 2020 Jun 18.

Abstract

Well-differentiated/dedifferentiated (WD/DD) liposarcomas, the most common form of liposarcomas, constitute up to 20 % of all soft tissue sarcomas. Several oncogenes are thought to be involved in liposarcoma pathogenesis, mainly MDM2, CDK4 and HMGA2. While MDM2 inhibitors are now tested in clinical trials, a second actionable and promising target appears to be cyclin-dependent kinase 4 (CDK4), which is amplified in up to 90 % of well differentiated or dedifferentiated (WD/DD) liposarcoma. With the paucity of available therapeutic options, the inhibition of CDK4 represent a potential therapeutic option. In this paper, we review the role of CDK4/6 inhibitors in targeting the commonly identified CDK4 amplification in WD/DD liposarcoma, with an emphasis on the published and currently ongoing trials.

Keywords: Abemaciclib; CDK4; Liposarcoma; MDM2; Palbociclib; Ribociclib; Soft tissue sarcoma.

Publication types

  • Review

MeSH terms

  • Cyclin-Dependent Kinase 4
  • Cyclins
  • Gene Amplification
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liposarcoma / drug therapy*
  • Liposarcoma / genetics*
  • Proto-Oncogene Proteins c-mdm2 / genetics*

Substances

  • Cyclins
  • Proto-Oncogene Proteins c-mdm2
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4