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

Overview

This study identifies a novel aggressive pancreatic cancer subtype characterized by high levels of nuclear GSK3β and NFATc1, which is associated with poor survival and early recurrence.

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options and a poor prognosis. Identifying molecular subtypes and their associated therapeutic vulnerabilities is crucial for improving patient outcomes. The GSK3βhigh/NFATc1high subtype is correlated with therapy resistance and aggressive tumor behavior.

Data Highlights

No numerical data was provided in the source material.

Key Findings

Nuclear GSK3β-NFATc1 signaling defines a highly aggressive PDAC subtype.
This subtype predicts early recurrence and poor survival following surgical resection.
Inactivation of GSK3β-NFATc1 signaling impairs homologous recombination (HR) repair mechanisms.
Targeting this signaling pathway may enhance the efficacy of cisplatin in GSK3βhigh/NFATc1high PDAC.

Clinical Implications

Understanding the GSK3βhigh/NFATc1high subtype may assist in predicting patient outcomes.

Conclusion

The identification of the GSK3βhigh/NFATc1high subtype provides insights into the mechanisms of therapy resistance in PDAC.

Targeting the GSK3βhigh/NFATc1high Subtype to Overcome Therapy Resistance in Pancreatic Cancer via Induction of Homologous Recombination Repair Mechanisms