Peer-reviewed article
DIPG-83. USING COPPER CHELATING AGENTS TO TARGET RECEPTOR TYROSINE KINASE SIGNALLING IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Michniewicz F, Saletta F, Rouen J, Ziegler D, Vittorio O ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a laboratory study investigating how copper chelating agents might be used to treat diffuse intrinsic pontine glioma (DIPG), a fatal pediatric brain cancer. The researchers tested a copper chelator called TEPA on cancer cells in culture and found it reduced cell growth by affecting signaling pathways. While the work involves children as the disease occurs in pediatric patients, it is basic laboratory research on cell lines, not an evaluation of outcomes for actual children.
Key points
- DIPG is a universally fatal pediatric brain cancer with frequent receptor tyrosine kinase pathway alterations
- Copper chelating agents like TEPA reduced DIPG cell proliferation in laboratory tests
- TEPA treatment reduced phosphorylated expression of AKT, ERK1/2, ERK5 and STAT3 proteins in cancer cells
- TEPA combined with Everolimus and Trametinib showed synergistic effects on target proteins
- The study proposes copper chelators as potential anti-cancer treatment candidates for DIPG
Limitations
This is in vitro laboratory research using cancer cell lines only, with no animal models, clinical trials, or outcomes data from children with DIPG. The findings cannot tell us whether this approach would be safe or effective in actual patients.
Abstract
Abstract DIPG is a universally fatal pediatric brain cancer. Receptor tyrosine kinase (RTK) pathway alterations are among the defining characteristics in many patients. Copper is a transition metal essential for cellular signaling, known to impact PI3K/AKT and MAPK/ERK pathways. Copper chelating agents are clinically approved for use in children with Wilson’s Disease, documented to reduce brain copper levels and are cited as potential cancer therapeutics. Due to copper’s wide cellular integration, we propose that targeting copper in DIPG through use of copper chelators is a viable therapeutic strategy and are strong candidates for combination therapy. Cytotoxicity assays performed in a panel of DIPG cell lines using copper chelator tetraethylenepentamine (TEPA) demonstrated a millimolar range of efficacy. To identify copper integrated pathways, western blots were performed on DIPG cell lines dosed with sub-lethal copper concentrations, which increased phosphorylated expression of AKT, ERK1/2, ERK5 and STAT3. Conversely, western blots performed after TEPA treatment demonstrated reduced phosphorylated expression of all these proteins compared to controls. Western blots investigating TEPA in combination with Everolimus and Trametinib demonstrated synergistic targeting of these proteins. Our results indicate that adding copper in the culture media initiated two RTK-mediated downstream signal transductions, including AKT and ERK and additionally STAT signaling. The use of copper chelator TEPA affected copper homeostasis and reduced DIPG cell proliferation. Our study proposes copper plays an important role in RTK-mediated signaling promoting DIPG proliferation. This implies that reducing copper with clinically available chelation agents can represent a potential anti-cancer treatment for DIPG.