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Omics · study · 2026

Targeting DHFR to suppress 1-C metabolism and enhance radiation sensitivity in NRF2-active head and neck squamous cell carcinoma

Listed in NCBI GEO

NRF2 hyperactivity is associated with radiation resistance in head and neck squamous cell carcinoma (HNSCC).

Description

We evaluated the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and its potent analog, WCDD115, as radiosensitizing agents through disruption of one-carbon metabolism.Preclinical studies used NRF2-competent and deficient HNSCC models, clonogenic assays, transcriptomics, metabolomics, pharmacokinetics/toxicity testing, and syngeneic tumor grafts to assess WCDD115 as a novel radiosensitizing agent.

Correlative analysis included mass spectrometry, western blotting, and pathway analysis. WCDD115 enhanced radiation-induced DNA damage and suppressed one-carbon metabolism and nucleotide biosynthesis.

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Life Sciences
Inferred from text
Cancer 65% · Mass spectrometry 75%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE34551514 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:mass-spectrometryenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title