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The Emerging Role of Transcription-Associated Cyclin-Dependent Kinases in Gastrointestinal Tumors

Dipti Athavale1, David Pulipati1, Curt Balch1

  • 1Coriell Institute for Medical Research, 403 Haddon Ave., Camden, NJ 08103, USA.

Cancers
|March 28, 2026
PubMed

Insights

Transcription-associated cyclin-dependent kinases (tCDKs) drive cancer growth by activating super enhancers. Targeting tCDKs offers new therapeutic strategies for gastrointestinal cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Disrupted transcriptional control is a hallmark of many cancers.
  • Transcription-associated cyclin-dependent kinases (tCDKs) regulate gene transcription via RNA polymerase II phosphorylation.

Purpose of the Study:

  • To review the role of tCDKs in gastrointestinal (GI) tumors.
  • To explore tCDKs as therapeutic targets in GI malignancies.

Main Methods:

  • Literature review of research studies on tCDKs in esophageal, gastric, pancreatic, and hepatobiliary cancers.
  • Analysis of tCDK involvement in super enhancer (SE) activation and "transcriptional addiction".

Main Results:

  • tCDKs activate SE regions, driving cancer cell growth and creating therapeutic vulnerabilities.
  • Increased tCDK expression is observed in GI tumor tissues, suggesting they are viable therapeutic targets.

Conclusions:

  • Targeting tCDKs, through genetic manipulation, small-molecule inhibitors, or protein degradation, presents promising therapeutic avenues for GI cancers.
  • Key challenges and future directions in tCDK-targeted therapy are discussed.
Keywords:
RNA polymerase IIgastrointestinal cancersinhibitorsresistancesuper enhancertoxicitytranscription-associated cyclin-dependent kinases

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