ArticleCancer chemotherapy and pharmacology2021
Probenecid increases renal retention and antitumor activity of DFMO in neuroblastoma.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Current status, hotspots and frontiers of ion channel-related research in glioblastoma: a bibliometric analysis from 2005 to 2024.Frontiers in oncology · 2025Review
- Bachmann-Bupp syndrome and treatment.Developmental medicine and child neurology · 2024Review
- Polyamines: their significance for maintaining health and contributing to diseases.Cell communication and signaling : CCS · 2023Review
- DMSO-tolerant ornithine decarboxylase (ODC) tandem assay optimised for high-throughput screening.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021Review
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNeuroblastoma (NB) is the most common extracranial solid tumor in children. Interference with the polyamine biosynthesis pathway by inhibition of MYCN-activated ornithine decarboxylase (ODC) is a validated approach. The ODC inhibitor α-difluoromethylornithine (DFMO, or Eflornithine) has been FDA-approved for the treatment of trypanosomiasis and hirsutism and has advanced to clinical cancer trials including NB as well as cancer-unrelated human diseases. One key challenge of DFMO is its rapid renal clearance and the need for high and frequent drug dosing during treatment.
methodsWe performed in vivo pharmacokinetic (PK), antitumorigenic, and molecular studies with DFMO/probenecid using NB patient-derived xenografts (PDX) in mice. We used LC-MS/MS, HPLC, and immunoblotting to analyze blood, brain tissue, and PDX tumor tissue samples collected from mice.
resultsThe organic anion transport 1/3 (OAT 1/3) inhibitor probenecid reduces the renal clearance of DFMO and significantly increases the antitumor activity of DFMO in PDX of NB (P < 0.02). Excised tumors revealed that DFMO/probenecid treatment decreases polyamines putrescine and spermidine, reduces MYCN protein levels and dephosphorylates retinoblastoma (Rb) protein (p-Rb
conclusionAddition of probenecid as an adjuvant to DFMO therapy may be suitable to decrease overall dose and improve drug efficacy in vivo.
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