CDK7 is a novel therapeutic target in fibrolamellar carcinoma

  • iScience. 2025 Nov 4;28(12):113925. doi: 10.1016/j.isci.2025.113925.
Manabu Nukaya  1 ,  Patrick R Carney  1 ,  Crystal Cafferty  1 ,  Katerina Zahed  1 ,  Isabelle Yun  1 ,  David P Al-Adra  2 ,  Noor A Kazim  3 ,  Alaa R Farghli  3 ,  Marina Chan  4 ,  Austin Stram  5 ,  Jeremy D Kratz  5 ,  Mark E Berres  6 ,  Andrew Yen  3 ,  Taranjit S Gujral  4 ,  Praveen Sethupathy  3 ,  Christopher A Bradfield  7 ,  Sean M Ronnekleiv-Kelly  1  8
Affiliations
  • 1. Department of Surgery, Division of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 2. Department of Surgery, Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 3. Cornell University College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY 14853, USA.
  • 4. Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • 5. Center for Human Genomics and Precision Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 6. Bioinformatics Resource Center, University of Wisconsin Biotechnology Center, Madison, WI 53792, USA.
  • 7. McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 8. University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
PMID: 41321622 DOI: 10.1016/j.isci.2025.113925
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.

Keywords
Biological sciences; Cancer; Cancer systems biology; Natural sciences; Systems biology.
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