TOP1
Overview
TOP1 (DNA Topoisomerase I) encodes the enzyme that relaxes supercoiled DNA by transiently cleaving one strand. It is the direct target of topoisomerase I inhibitors (irinotecan/SN-38, topotecan), which trap the covalent TOP1-DNA intermediate and cause replication-associated double-strand breaks. SLFN11 expression has emerged as a co-predictive biomarker for sensitivity to TOP1 inhibitors across cancer lineages.
Alterations observed in the corpus
- TOP1 is the target enzyme of irinotecan and topotecan; its expression and activity underlie the mechanism of action of these agents profiled in the Cancer Cell Line Encyclopedia (947 cell lines, 24 drugs) PMID:22460905
- TOP1 expression and copy number variation in NCI-60 cell lines correlated with topotecan sensitivity in CellMiner pharmacogenomics analysis PMID:22802077
Cancer types (linked)
- No cancer-type-specific prevalence or mutation data in the current corpus.
Co-occurrence and mutual exclusivity
- SLFN11 expression is the top predictive biomarker for sensitivity to TOP1-targeting drugs (irinotecan, topotecan) across cancer cell lines; the two genes functionally interact in the context of DNA damage response PMID:22460905
Therapeutic relevance
- TOP1 is the molecular target of irinotecan (prodrug SN-38) and topotecan; large-scale pharmacogenomic profiling across 947 cell lines confirms lineage- and biomarker-stratified sensitivity to these agents PMID:22460905
Open questions
- Whether TOP1 copy number or expression level independently predicts sensitivity to TOP1 inhibitors beyond SLFN11 expression has not been evaluated in this corpus.
Sources
This page was processed by entity-page-writer on 2026-05-06. - PMID:22802077
This page was processed by wiki-cli on 2026-05-06.