# Topoisomerase I (TOP1)

Source: https://onco.cc/targets/top1/  
OnCo record `top1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The enzyme that nicks one DNA strand to relieve twisting while DNA is copied. Camptothecins and the payloads of several antibody-drug conjugates trap it on the DNA so the nick becomes a permanent break when the cell replicates.

## Summary

Topoisomerase I relaxes supercoiled DNA by cutting one strand, letting it rotate and resealing it. Camptothecin derivatives such as irinotecan, topotecan, SN-38, DXd and exatecan bind the enzyme-DNA complex and stop the reseal step, so replication forks collide with the trapped complex and create double-strand breaks. The same chemistry is the payload of sacituzumab govitecan, trastuzumab deruxtecan and datopotamab deruxtecan, which explains their shared toxicities of neutropenia and diarrhoea and the cross-resistance seen when one topoisomerase I antibody-drug conjugate follows another.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Symbol: TOP1
- Class: enzyme
- Biology: Type IB topoisomerase that relieves torsional stress during replication and transcription; trapped as a covalent cleavage complex by camptothecins.
- Where found: Expressed in all dividing cells; relevant wherever camptothecin or topoisomerase I payload drugs are used

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/TOP1
- UniProt P11387: TOP1: https://www.uniprot.org/uniprotkb/P11387/entry

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [HR070803](https://onco.cc/drugs/hr070803/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Topotecan](https://onco.cc/drugs/topotecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- trials: [First-in-Human Study of ADCE-D01 in Soft Tissue Sarcoma](https://onco.cc/trials/nct06797999/)
- targets: [B7-H4 (VTCN1)](https://onco.cc/targets/b7h4/)

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JSON: https://onco.cc/api/v1/entities/top1.json