fluorouracil

Overview

5-Fluorouracil, thymidylate synthase-inhibiting antimetabolite; backbone of FOLFOX/FOLFIRI/FOLFIRINOX.

Evidence in the corpus

  • Listed among colorectal-style first-line regimens (FOLFOX/FOLFIRI/FOLFIRINOX) applied to appendiceal adenocarcinoma; GNAS-mut predominant MAAP patients had only a 6% first-line response rate to such 5-FU-based therapy vs 50% for RAS-mut predominant MAAP (P=.03) PMID:36493333.
  • KRASG12R-mutant pancreatic adenocarcinoma (PAAD) patients showed enrichment among those receiving neoadjuvant chemotherapy (most frequently FOLFIRINOX: fluorouracil + irinotecan + oxaliplatin + leucovorin) followed by resection (32.7% vs 17.9% for KRASG12D, p=0.094), suggesting potentially greater fluorouracil-based chemosensitivity in KRASG12R tumors PMID:39214094.
  • FOLFIRINOX (fluorouracil + irinotecan + oxaliplatin + leucovorin) was administered to 38% of the 1,480-patient MSK PDAC cohort as first-line systemic therapy; chemotherapy backbone choice between FOLFIRINOX and gemcitabine/nab-paclitaxel was not significantly associated with OS in the 304 metastatic chemotherapy-treated patients PMID:39753968.
  • Synergizes with prexasertib (CHEK1 inhibitor) in FBXO7-deficient colorectal cancer cells within a defined concentration window (1.92–9.6 nM prexasertib + 28 micromolar 5-FU; Loewe Additivity model); antagonistic at lower 5-FU concentrations PMID:36334560
  • Listed as a component of standard head and neck cancer systemic therapy regimens in the cBioPortal platform paper describing HNSCC genomic data PMID:19176454
  • Cited in HCC systemic therapy review as a reference chemotherapy agent in historical combination regimens PMID:24798001
  • Implicated in standard chemotherapy regimens for gastric adenocarcinoma (STAD); high-clonality (HiC) GC subtype (adjusted HR 4.69, P=0.0043 for shorter survival) and subclonal TP53 suggest single-agent regimens may select for resistant clones PMID:25583476
  • Listed among concurrent systemic therapies used in SBRT trials for locally advanced PAAD, alongside gemcitabine and capecitabine; the Koong et al Phase II (n=16, 45 Gy IMRT + 25 Gy SBRT boost + 5-FU) achieved 94% 1-year freedom from local recurrence with 13% grade 3+ acute toxicity PMID:27826200
  • Fluorouracil-containing regimens (FOLFOX, FOLFIRI, capecitabine-containing) were used as standard first-line chemotherapy in the 295-patient metastatic EGC cohort; MSI-H patients showed inferior PFS on cytotoxic regimens (4.8 vs 6.9 months, HR=0.4, P=0.027) PMID:29122777

Resistance mechanisms

  • GNAS-mut predominant molecular subtype of mucinous appendiceal adenocarcinoma associates with 5-FU-based chemotherapy resistance PMID:36493333.

Cancer types (linked)

  • APAD
  • PAAD — pancreatic adenocarcinoma (FOLFIRINOX backbone, allele-specific chemosensitivity signal)

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:19176454

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:25583476

This page was processed by crosslinker on 2026-05-14. - PMID:29122777

This page was processed by wiki-cli on 2026-05-15.