Pansarcoma Analysis of Cyclin-Dependent Kinase and Cyclin Outlier Gene Expression Highlights CDK7 as a Potential Therapeutic Target in Chordoma.

Publication/Presentation Date

7-1-2025

Abstract

PURPOSE: Cyclin-dependent kinase (CDK)4/6 inhibitors are approved for the treatment of breast cancer, and they have more recently been used in patients with well-differentiated/dedifferentiated liposarcomas (WD-LPSs/DD-LPSs). However, targeting of these and other CDKs, including transcriptional CDKs, remains a promising avenue of investigation for various cancers. Therefore, we sought to characterize outlier overexpression of CDK and cyclin genes in sarcomas. On the basis of the initial results, further studies were undertaken to investigate the roles of CDK7 and CDK18 in chordomas.

MATERIALS AND METHODS: An initial analysis of CDK/cyclin gene expression involved an American national biomarker database of deidentified patients (Caris Life Sciences, Phoenix, AZ; n = 3,757) using novel, strict definitions to identify outlier overexpressing samples across subtypes. Results were validated with a German national database (Molecularly Aided Stratification for Tumor Eradication Research [MASTER]; n = 943). Outlier overexpression for

RESULTS: Initial analysis identified expected findings (eg, outlier overexpression of

CONCLUSION: This study supports further investigation into targeting of CDKs and cyclins in select sarcoma subtypes, and it specifically suggests a therapeutic approach inhibiting CDK7 in chordoma.

Volume

9

First Page

2500149

Last Page

2500149

ISSN

2473-4284

Disciplines

Medicine and Health Sciences

PubMedID

40601892

Department(s)

Hematology-Medical Oncology Division

Document Type

Article

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