Targeting ErbB3 in Pancreatic Cancer
Author Information
Author(s): Liles J S, Arnoletti J P, Kossenkov A V, Mikhaylina A, Frost A R, Kulesza P, Heslin M J, Frolov A
Primary Institution: University of Alabama at Birmingham
Hypothesis
Cancer-associated fibroblasts (CAF) secrete NRG-1 ligand, which in turn activates cancer cell ErbB3/AKT-mediated signalling, promoting tumourigenesis and rendering EGFR inhibition ineffective.
Conclusion
Disruption of the stromally mediated tumourigenic mechanism is best obtained through combined EGFR-ErbB3 inhibition with both erlotinib and MM-121.
Supporting Evidence
- CAF secreted NRG-1 promotes proliferation in pancreatic cancer cells.
- Combined treatment with MM-121 and erlotinib significantly inhibits tumour growth.
- CAF-containing xenografts showed greater tumour volume compared to those without CAF.
Takeaway
Cancer cells in the pancreas can grow faster because of signals from nearby fibroblast cells, and blocking these signals can help stop the cancer from growing.
Methodology
Primary CAF cultures were established from human PDAC surgical specimens, and AsPC-1 pancreatic cancer cell murine subcutaneous xenografts were developed and treated with EGFR and ErbB3 inhibitors.
Potential Biases
Potential bias in the selection of patient specimens and the interpretation of results based on specific experimental conditions.
Limitations
The study primarily focuses on the role of NRG-1 and ErbB3, potentially overlooking other factors influencing pancreatic cancer progression.
Participant Demographics
Patients with pancreatic ductal adenocarcinoma who underwent surgical treatment.
Statistical Information
P-Value
p<0.001
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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