PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy-induced senescence Academic Article uri icon

Overview

MeSH Major

  • Carcinoma
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Gene Deletion
  • Homozygote
  • Sarcoma
  • Tissue Banks
  • Transcription Factors

abstract

  • CDK4/6 inhibitors are being used to treat a variety of human malignancies. In well-differentiated and dedifferentiated liposarcoma their clinical promise is associated with their ability to downregulate the MDM2 protein. The downregulation of MDM2 following treatment with CDK4/6 inhibitors also induces many cultured tumor cell lines derived from different types of malignancies to progress from quiescence into senescence. Here we used cultured human cell lines and defined a role for PDLIM7 and CDH18, regulating MDM2 protein in CDK4/6 inhibitor-treated cells. Materials from our previous phase II trials with palbociclib were then used to demonstrate that expression of CDH18 protein was associated with response, measured as both progression-free survival and overall survival. This supports the hypothesis that the biologic transition from quiescence to senescence has clinical relevance for this class of drugs.

publication date

  • May 23, 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/s41388-018-0332-y

PubMed ID

  • 29789718

Additional Document Info

start page

  • 1

end page

  • 13