<unk>  is a semi-synthetic derivative of camptothecin. Camptothecin is a natural product extracted from the bark of the tree Camptotheca acuminata. Topoisomerase-I is a nuclear enzyme that relieves torsional strain in DNA by opening single strand breaks. Once topoisomerase-I creates a single strand break, the DNA can rotate in front of the advancing replication fork. In physiological environments,<unk>  is in equilibrium with its inactive carboxylate form.<unk> 's active lactone form intercalates between DNA bases in the topoisomerase-I cleavage complex. The binding of<unk>  in the cleavage complex prevents topoisomerase-I from religating the nicked DNA strand after relieving the strain. This intercalation therefore traps the topoisomerase-I in the cleavage complex bound to the DNA. When the replication-fork collides with the trapped topoisomerase-I, DNA damage occurs. The unbroken DNA strand breaks and mammalian cells cannot efficiently repair these double strand breaks. The accumulation of trapped topoisomerase-I complexes is a known response to apoptotic stimuli. This disruption prevents DNA replication and ultimately leads to cell death. This process leads to breaks in the DNA strand resulting in apoptosis. Administration of<unk>  down-regulates its target, topoisomerase-I; therefore, it is dosed to maximize efficacy and minimize related toxicity.<unk>  is often given in combination with paclitaxel as first line treatment for extensive-stage small-cell lung cancer.
Topotecan
Ifosfamide
Irinotecan
Vincristine
Normustine
Etoposide
Doxorubicin
Bendamustine