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Pansarcoma Analysis of Cyclin-Dependent Kinase and Cyclin Outlier Gene Expression Highlights CDK7 as a Potential

Daniel S Lefler1, Andrew Elliott2, Wei Jiang3

  • 1Department of Medicine, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

JCO Precision Oncology
|July 2, 2025
PubMed
Abstract

Insights

This study identified outlier overexpression of CDK7 and CDK18 in chordomas, suggesting CDK7 inhibition as a potential therapeutic strategy for this rare cancer. Further research into targeting CDKs and cyclins in sarcomas is warranted.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cyclin-dependent kinase (CDK)4/6 inhibitors are established treatments for breast cancer.
  • CDK inhibitors are being explored for various cancers, including liposarcomas.
  • Targeting transcriptional CDKs presents a promising therapeutic avenue in oncology.

Purpose of the Study:

  • To identify outlier overexpression of cyclin-dependent kinase (CDK) and cyclin genes across sarcoma subtypes.
  • To investigate the specific roles of CDK7 and CDK18 in chordoma.
  • To evaluate the therapeutic potential of CDK7 inhibition in chordoma.

Main Methods:

  • Analysis of CDK/cyclin gene expression in large national biomarker databases (n=3,757 and n=943).
  • Identification of outlier overexpression using strict definitions.
  • Validation of findings using immunohistochemistry (IHC) and testing of a CDK7 inhibitor in chordoma cell lines.

Main Results:

  • Identified outlier overexpression of CDK4 in liposarcomas and CCND1 in Ewing sarcomas.
  • Discovered significant outlier overexpression of CDK7 (42%) and CDK18 (37%) in chordomas.
  • Confirmed CDK7/18 overexpression via IHC and demonstrated high efficacy of CDK7 inhibition in chordoma cell lines.

Conclusions:

  • Further investigation of CDK and cyclin targeting in specific sarcoma subtypes is supported.
  • CDK7 inhibition is a promising therapeutic strategy for chordoma.
  • This study highlights novel associations and potential therapeutic targets in sarcoma treatment.

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