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difluoromethylornithine + celecoxib + cyclophosphamide + topotecan
- Development stage
- Phase 1
- Lead developer
- New Advances in Neuroblastoma Therapy Consortium
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This therapeutic regimen is an experimental combination therapy being evaluated for the treatment of relapsed or refractory high-risk neuroblastoma. The combination consists of **difluoromethylornithine (DFMO)**, an irreversible inhibitor of ornithine decarboxylase (ODC) that depletes intracellular polyamines; **celecoxib**, a selective cyclooxygenase-2 (COX-2) inhibitor; and a cytotoxic chemotherapy backbone of **cyclophosphamide** (an alkylating agent) and **topotecan** (a topoisomerase I inhibitor). The rationale for this combination is based on the observation that polyamine synthesis and COX-2 pathways are often upregulated in neuroblastoma and contribute to tumor progression and chemoresistance. By targeting these metabolic and inflammatory pathways alongside standard DNA-damaging agents, the regimen aims to overcome resistance and improve clinical outcomes in pediatric patients with difficult-to-treat neuroblastoma.
- Other names
- DFMO + celecoxib + cyclophosphamide + topotecanEflornithine + celecoxib + cyclophosphamide + topotecan
02
Targets
DNATOP1 (DNA Topoisomerase I)PTGS2 (Prostaglandin-Endoperoxide Synthase 2)ODC1 (Ornithine decarboxylase)
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