CDK7 is a novel therapeutic target in fibrolamellar carcinoma

Fibrolamellar Carcinoma (FLC) is a rare and deadly cancer that arises in young, otherwise healthy patients. For patients that cannot be treated with surgery, only 30%-45% survive to 5 years with current treatment options. These poor survival odds highlight the need for new therapeutic targets. Using patient samples, we identified that abnormal function of cyclin-dependent kinase 7 (CDK7) is a key component of pathways that are essential for FLC cancer cell identity and survival. Consequently, drug inhibitors of CDK7 suppressed these abnormal pathways and also caused cancer cell death in a dose-dependent manner. This held true in several patient-derived models of FLC. We then found that inhibition of CDK7 can combine with other drug candidates to increase the therapeutic response in FLC cells. Taken together, this suggests CDK7 is a promising target for future treatment in human FLC.

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Publication Details

Journal
iScience
Published
2025-11-05
DOI
https://doi.org/10.1016/j.isci.2025.113925
Primary Topic
Cancer-related Molecular Pathways
Type
article
Field-Weighted Citation Impact
0.00
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article

CDK7 is a novel therapeutic target in fibrolamellar carcinoma

Katerina Zahed, Jeremy D. Kratz, Taranjit S. Gujral, Christopher A. Bradfield et al.
iScience
Cancer-related Molecular Pathways
article

CDK7 is a novel therapeutic target in fibrolamellar carcinoma

Katerina Zahed, Jeremy D. Kratz, Taranjit S. Gujral, Christopher A. Bradfield, Noor A. Kazim, Andrew Yen, Sean M. Ronnekleiv‐Kelly, David Al‐Adra, Patrick R. Carney, Isabelle Yun, Alaa R. Farghli, Crystal Cafferty, Praveen Sethupathy, Mark E. Berres, Austin Stram, Manabu Nukaya, Marina Chan
article en

Abstract

Fibrolamellar Carcinoma (FLC) is a rare and deadly cancer that arises in young, otherwise healthy patients. For patients that cannot be treated with surgery, only 30%-45% survive to 5 years with current treatment options. These poor survival odds highlight the need for new therapeutic targets. Using patient samples, we identified that abnormal function of cyclin-dependent kinase 7 (CDK7) is a key component of pathways that are essential for FLC cancer cell identity and survival. Consequently, drug inhibitors of CDK7 suppressed these abnormal pathways and also caused cancer cell death in a dose-dependent manner. This held true in several patient-derived models of FLC. We then found that inhibition of CDK7 can combine with other drug candidates to increase the therapeutic response in FLC cells. Taken together, this suggests CDK7 is a promising target for future treatment in human FLC.

iScienceVol. 28(12)
University of Wisconsin–Madison (US), Cornell University (US), Fred Hutch Cancer Center (US), New York State College of Veterinary Medicine (US)
Openalex Percentile: Top 56%
Cancer-related Molecular Pathways
DOIOpen Access PDFOpenAlex
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CDK7 is a novel therapeutic target in fibrolamellar carcinoma — Katerina Zahed, Jeremy D. Kratz, et al. · iScience (2025) | TGRS Research Map | TGRS