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Updated: Feb 10, 2026
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Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
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NRG1 Fusions in KRAS Wild-Type Pancreatic Cancer
Christoph Heining1,2,3,4, Peter Horak5,6,7, Sebastian Uhrig7,8,9
1Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany.
Cancer Discovery
|May 27, 2018
Summary
Identifying gene fusions in young adults with pancreatic cancer (PDAC) revealed new treatment targets. Targeting NRG1 rearrangements with ERBB inhibitors led to remission in patients with KRAS wild-type tumors.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options.
- Molecularly targeted therapies for PDAC are lacking, particularly for younger patients.
- Precision oncology approaches are needed to identify actionable genomic alterations.
Purpose of the Study:
- To identify clinically actionable genomic alterations in young adults with PDAC.
- To investigate the role of gene fusions in PDAC development and progression.
- To evaluate the efficacy of targeted therapies against identified genomic alterations.
Main Methods:
- Whole-genome and transcriptome sequencing of 17 PDAC patients.
- Molecular characterization of tumors within a precision oncology program.
- Pharmacologic inhibition of identified aberrant signaling pathways.
Main Results:
- All KRAS wild-type (KRASWT) PDAC tumors (4/17) harbored actionable gene fusions.
- Recurrent NRG1 rearrangements were identified as drivers of PDAC via ERBB signaling.
- ERBB inhibition led to clinical improvement and remission of liver metastases in 2 patients with NRG1-rearranged tumors resistant to standard treatment.
Conclusions:
- Systematic screening for oncogenic fusion genes in KRASWT PDAC can improve therapeutic outcomes.
- NRG1 fusions represent a novel class of disease-driving events in PDAC.
- Targeting ERBB signaling offers a promising therapeutic strategy for a subset of PDAC patients.
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