TY  - JOUR
AU  - Lefler, Daniel S.
AU  - Elliott, Andrew
AU  - Jiang, Wei
AU  - Martinez-Outschoorn, Ubaldo
AU  - Al-Sabah, Jude
AU  - Freed, Daniel M.
AU  - King, Caitlin M.
AU  - Maki, Robert G.
AU  - Riedel, Richard F.
AU  - Modiano, Jaime F.
AU  - Hübschmann, Daniel
AU  - Glimm, Hanno
AU  - Fröhling, Stefan
AU  - Oberley, Matthew
AU  - Boikos, Sosipatros A.
AU  - Basu Mallick, Atrayee
TI  - Pansarcoma Analysis of Cyclin-Dependent Kinase and Cyclin Outlier Gene Expression Highlights CDK7 as a Potential Therapeutic Target in Chordoma
JO  - JCO precision oncology
VL  - 9
SN  - 2473-4284
CY  - Alexandria, VA
PB  - American Society of Clinical Oncology
M1  - DKFZ-2025-01347
SP  - e2500149
PY  - 2025
N1  - 2025 Jul:9:e2500149
AB  - 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 CDK7/18 in chordoma was compared with immunohistochemical (IHC) expression using tissue microarrays, and a selective investigational CDK7 inhibitor was tested against four chordoma cell lines.Results: Initial analysis identified expected findings (eg, outlier overexpression of CDK4 in 39
LB  - PUB:(DE-HGF)16
C6  - pmid:40601892
DO  - DOI:10.1200/PO-25-00149
UR  - https://inrepo02.dkfz.de/record/302807
ER  -