topoisomerase inhibitor

A topoisomerase inhibitor is a cancer drug that sabotages the enzymes which keep DNA from tangling. DNA is an immensely long double helix crammed into a tiny cell, and every time it is copied or read it twists and knots like an over-wound phone cord. Topoisomerases are the enzymes that nick the DNA, let it swivel to relieve the tension, and then reseal it. Block them and a dividing cell drowns in its own snarled DNA.

Many of these drugs do something subtler than simply switching the enzyme off — they freeze it in the middle of its job. Topoisomerases work by transiently cutting the DNA strand; the drug traps the enzyme while the DNA is still cut, leaving a permanent break. For a cell trying to replicate, these stranded broken ends are catastrophic and tip it into programmed cell death.

Because they ride on the universal need to manage DNA, topoisomerase inhibitors are potent against many cancers but, like other DNA-directed drugs, they damage healthy dividing cells and carry a long-term risk of causing secondary cancers. Their punch and reliable cell-killing also make them favored payloads to load onto antibody-drug conjugates for more selective delivery.