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# Topoisomerase inhibitors

Cancer drugs that trap the enzymes that cut and reseal DNA. The cut DNA stays open and turns into breaks that kill dividing cells.

Updated 2026-11-01

## What they are

Topoisomerase I inhibitors (camptothecins: irinotecan, topotecan) and topoisomerase II inhibitors (epipodophyllotoxins: etoposide). Anthracyclines also poison topoisomerase II but are grouped with the antitumour antibiotics.

## Mechanism of action

Topoisomerases relieve the twisting of DNA during replication by cutting it and resealing it. Camptothecins bind the topoisomerase I–DNA complex and prevent resealing of the single-strand nick; etoposide does the same with topoisomerase II and its double-strand cut. When the replication fork runs into these trapped complexes, permanent double-strand breaks form and the cell undergoes apoptosis.

Target: DNA topoisomerase I or II

## Key points

- Topoisomerase I: irinotecan and topotecan. Topoisomerase II: etoposide (and the anthracyclines).
- Irinotecan: early cholinergic diarrhoea (responds to atropine) and late, severe diarrhoea; risk of neutropenia rises with UGT1A1*28 or *6 variants.
- Etoposide: myelosuppression, hypotension if infused too fast, and secondary leukaemia.
- Topotecan: severe myelosuppression is the main toxicity.

## Drugs in this class

- [**Etoposide** A plant-derived drug that traps topoisomerase II on cut DNA. Used in testicular and small cell lung cancer; its main… DNA topoisomerase IIα](https://durgical.com/en/pharmacology/etoposide/)
- [**Irinotecan** A camptothecin prodrug for colorectal cancer. Its active form SN-38 traps topoisomerase I; early and late diarrhoea… DNA topoisomerase I](https://durgical.com/en/pharmacology/irinotecan/)
- [**Topotecan** A camptothecin that traps topoisomerase I. Used in relapsed ovarian and small cell lung cancer and in cervical cancer… DNA topoisomerase I](https://durgical.com/en/pharmacology/topotecan/)

## Others in the class

- teniposide
- belotecan

## Test yourself

Think of the answer, then tap the question to see it.

## Which topoisomerase do irinotecan and topotecan inhibit, and which does etoposide inhibit?

Irinotecan and topotecan: topoisomerase I. Etoposide: topoisomerase II.

## Why are topoisomerase poisons more toxic to dividing cells?

The trapped enzyme–DNA complexes become permanent double-strand breaks when the replication fork reaches them.

## Which gene variant raises the risk of severe neutropenia with irinotecan?

Reduced-function UGT1A1 alleles (*28 or *6), which slow the inactivation of SN-38.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - ETOPOSIDE injection, solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe870629-104d-4d67-a7c6-f53bc588121e) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - IRINOTECAN HYDROCHLORIDE injection, solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c527c2e-9062-4afe-dbbb-f650db3a340f) (DailyMed (U.S. National Library of Medicine), 2025); [DailyMed - TOPOTECAN HYDROCHLORIDE injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6019088-cd94-43b4-b5ce-ba20b6b8021e) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 70 (McGraw Hill, 2023).

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