GSK3βhigh/NFATc1high subtype targeting overcomes therapy resistance in pancreatic cancer through transcriptional induction of homologous recombination repair - Summary - MDSpire
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Targeting the GSK3βhigh/NFATc1high Subtype to Overcome Therapy Resistance in Pancreatic Cancer via Induction of Homologous Recombination Repair Mechanisms

  • By

  • Muhammad Umair Latif

  • Xueang Liu

  • Aiko Bockelmann

  • Laura Huhnold

  • Geske Elisabeth Schmidt

  • Lukas Klein

  • Xueyuan Zhao

  • Lena-Christin Conradi

  • Karly Conrads

  • Anna Lena Weber

  • Sercan Mercan

  • Kristina Reutlinger

  • Atmika Paul

  • Zeynab Najafova

  • Steven A Johnsen

  • Zuriñe Bonilla Del Rio

  • Frederike Penz

  • Jovan Todorovic

  • Holger Bastians

  • Tim Beissbarth

  • Ulrich Sax

  • Ramy Ashry

  • Oliver H Krämer

  • Elisabeth Hessmann

  • Günter Schneider

  • Philipp Stroebel

  • Ivan Bogeski

  • Shiv K Singh

  • Volker Ellenrieder

  • August 1, 2026

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Objective:

To investigate the role of nuclear GSK3β-NFATc1 signaling in pancreatic ductal adenocarcinoma (PDAC) and its association with therapy resistance and tumor recurrence.

Approach:
  • Study Design: The study utilized publicly available datasets and clinical specimens from patients with resected PDAC to analyze the expression and localization of GSK3β and its impact on tumor behavior.
  • Molecular Analysis: The study identified a novel PDAC subtype characterized by high nuclear GSK3β and NFATc1 expression, termed GSK3βhigh/NFATc1high, and assessed its correlation with clinical outcomes.
  • Functional Experiments: Preclinical experiments were conducted to evaluate the effects of inhibiting GSK3β-NFATc1 signaling on homologous recombination (HR) repair mechanisms and the efficacy of cisplatin.
Key Findings:
  • The GSK3βhigh/NFATc1high PDAC subtype is associated with early recurrence and poor survival post-surgery.
  • Nuclear GSK3β enhances tumor growth and DNA repair by activating NFATc1-dependent transcription of HR repair genes.
  • Inhibition of GSK3β-NFATc1 signaling impairs HR and increases the effectiveness of cisplatin in GSK3βhigh/NFATc1high PDAC.
Interpretation:

Limitations:
  • The findings need validation in larger patient cohorts.
  • Further research is required to explore the clinical implications of targeting the GSK3β-NFATc1 axis.
Conclusion:

Original Source(s)

GSK3βhigh/NFATc1high subtype targeting overcomes therapy resistance in pancreatic cancer through transcriptional induction of homologous recombination repair

  • by Muhammad Umair Latif, Xueang Liu, Aiko Bockelmann, Laura Huhnold, Geske Elisabeth Schmidt, Lukas Klein, Xueyuan Zhao, Lena-Christin Conradi, Karly Conrads, Anna Lena Weber, Sercan Mercan, Kristina Reutlinger, Atmika Paul, Zeynab Najafova, Steven A Johnsen, Zuriñe Bonilla Del Rio, Frederike Penz, Jovan Todorovic, Holger Bastians, Tim Beissbarth, Ulrich Sax, Ramy Ashry, Oliver H Krämer, Elisabeth Hessmann, Günter Schneider, Philipp Stroebel, Ivan Bogeski, Shiv K Singh, Volker Ellenrieder

  • August 1, 2026

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