ArticleCancer medicine2025
Inhibition of Purine Metabolism Promotes the Differentiation of Neuroblastoma Driven by MYCN.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
backgroundNeuroblastoma (NB), the common extracranial solid tumor in children, is associated with a poor prognosis, particularly in high-risk patients. MYCN amplification stands as the most prominent molecular hallmark within this high-risk subgroup. However, MYCN protein is considered "undruggable" due to its lack of a conventional enzymatic binding pocket and its predominant nuclear localization, which precludes targeting by standard small-molecule inhibitors or antibody-based therapeutics. Consequently, current therapeutic strategies have achieved limited efficacy against MYCN-driven NB. Notably, MYCN not only orchestrates diverse metabolic reprogramming pathways in tumors but also exerts a pivotal influence on cellular differentiation. To overcome this therapeutic barrier, we seek to elucidate the contribution of purine metabolism to stemness maintenance in MYCN-amplified NBs and to discover novel small-molecule inhibitors capable of inducing differentiation in high-risk NBs.
methodsMetabolomic profiling via mass spectrometry was employed to delineate differential metabolite signatures between MYCN-amplified and non-amplified NB cells. Bioinformatics analysis of publicly available RNA sequencing datasets facilitated the systematic evaluation of purine metabolic enzyme expression. Cell differentiation, proliferation, colony formation, and cell migration assays were employed to assess the inhibitor's effects. Additionally, an in vivo xenograft model of NB was established to examine the therapeutic potential of lometrexol (LMX), a selective inhibitor of the purine biosynthesis enzyme phosphoribosylglycinamide formyltransferase (GART).
resultsSignificant changes in nucleotide metabolism were identified in NB cell lines with high MYCN expression compared to those with low MYCN expression. The expression of purine metabolic enzyme genes was positively correlated with MYCN expression, prognosis, and differentiation status in NBs. Pharmacological inhibition of GART using LMX elicited a robust pro-differentiation response, concomitant with a significant suppression of tumorigenic potential.
conclusionsThese findings establish purine metabolic enzyme inhibition as a viable therapeutic strategy to induce differentiation and attenuate tumor progression in high-risk MYCN-amplified NBs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.