mitomycin-c
Overview
Mitomycin C is a DNA cross-linking agent that exploits homologous recombination deficiency (HRD). It is particularly active in tumors with defects in the Fanconi anaemia/BRCA pathway, which are unable to repair interstrand cross-links. It is nominated alongside PARP inhibitors as a therapeutic strategy in pancreatic ductal adenocarcinoma with DNA repair gene inactivation.
Evidence in the corpus
- DNA repair deficiency (14% Fanconi-anaemia-pathway alterations including ATM, CHEK2, BRCA1, BRCA2, FANCA, FANCD2, FANCM; enriched in high-CNV clusters 5 and 6) in 109 resected pancreatic ductal adenocarcinomas nominates mitomycin C (cross-linking agent) alongside olaparib as therapeutic candidates; high-CNV clusters could serve as stratification biomarkers PMID:25855536
- Intravesical mitomycin C was used as adjuvant therapy in 39% of low-grade Ta (LGTa) nonmuscle invasive bladder cancer (NMIBC) patients in the MSK NMIBC cohort (n=23 LGTa); patients receiving perioperative mitomycin or other adjuvant perioperative therapies were excluded from index tumor sequencing to ensure pre-treatment genomic profiling. PMID:28583311
Resistance mechanisms
Cancer types (linked)
Sources
- PMID:25855536 — Waddell et al. 2015, Nature. Pancreatic ductal adenocarcinoma genomics; mitomycin C nominated for FA-pathway-deficient PDAC.
- PMID:28583311 — Pietzak et al. 2017, Cancer. MSK NMIBC MSK-IMPACT study; intravesical mitomycin C in 39% of LGTa patients; excluded from index sequencing.
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