topoisomerase inhibitor

A topoisomerase inhibitor blocks the enzymes that untangle DNA. DNA is a tightly wound double helix; to read or copy it, the cell must unwind and relax that coil without snapping the whole strand. Topoisomerases are the molecular scissors-and-tape that make a controlled cut, let the tension out, and reseal it. These drugs stop the resealing, leaving dangerous breaks.

There are two main targets. Topoisomerase I makes single-strand nicks; drugs like irinotecan and topotecan (camptothecin derivatives) trap the enzyme on the cut DNA so the break is never repaired. Topoisomerase II makes double-strand cuts; drugs such as etoposide and the anthracycline doxorubicin freeze it in the broken state. In both cases, the cell is left with permanent DNA breaks that trigger cell death, especially in rapidly replicating tumour cells.

An important caveat is that anthracyclines like doxorubicin carry a cumulative, dose-dependent risk of heart muscle damage, partly through mechanisms beyond topoisomerase II. Lifetime doses are therefore capped, and cardiac function is monitored. Some topoisomerase inhibitors, like alkylating agents, also raise the risk of treatment-related leukaemia.