Pharmacology · Class
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
Drugs in this class
- EtoposideA plant-derived drug that traps topoisomerase II on cut DNA. Used in testicular and small cell lung cancer; its main…DNA topoisomerase IIα
- IrinotecanA camptothecin prodrug for colorectal cancer. Its active form SN-38 traps topoisomerase I; early and late diarrhoea…DNA topoisomerase I
- TopotecanA camptothecin that traps topoisomerase I. Used in relapsed ovarian and small cell lung cancer and in cervical cancer…DNA topoisomerase I
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.
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 (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - IRINOTECAN HYDROCHLORIDE injection, solution (DailyMed (U.S. National Library of Medicine), 2025); DailyMed - TOPOTECAN HYDROCHLORIDE injection, powder, lyophilized, for solution (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 70 (McGraw Hill, 2023).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.