Topoisomerase Poisons

Topoisomerase is a specialised nuclear enzyme that is capable of causing single (topoisomerase I) or double (topoisomerase II) strand DNA breaks to allow two strands to DNA to uncoil or pass through each other. It is essential to the normal function of the cell and there are two forms, topoisomerase I and II. Poisons typically allow the break to occur but prevent repair of the damage, leading to a double strand break and cell death.

Topoisomerase I Poisons (irinotecan)

Irinotecan is commonly used for colorectal cancers in combination with folinic acid and 5-fluorouracil (FOLFIRI).

Mechanism of Action

Irinotecan binds to topoisomerase I, preventing DNA re-ligation during DNA replication. This causes double strand breaks and cell death. It is particularly active in S phase.

Side effects

Irinotecan typically causes neutropenia and may cause diarrhoea. Hair loss is not uncommon.

Interaction with Radiotherapy

Irinotecan is rarely used in conjunction with radiotherapy but toxicity does not seem to be excessive.

Topoisomerase II Poisons (Etoposide, Anthracyclines)

The anthracyclines fit here as well as in the Antibiotic topic, where they are covered in detail.
Etoposide is commonly used in lung cancer (both small cell and non-small cell) in combination with platinum chemotherapy.

Mechanism of Action

Etoposide binds to topoisomerase II, causing double strand DNA breaks and cell death.

Side effects

The main toxicity is neutropenia. Unlike topoisomerase I poisons, etoposide has minimal side effects. Oral administration causes nausea and vomiting.

Interaction with radiotherapy

There appears to be minimal cross reactivity.