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What do Type I and Type II topoisomerases usually do?
Type I - cuts single stranded DNA
Type II - cuts double stranded DNA
True or False. Topoisomerase is absolutely necessary for cell viability.
How do topoisomerase inhibitors work?
Inhibit activity of topoisomerase, blocks the ligation of the cell cycle.
How does Camptothecin work? What part of the cell cycle does it work on?
Inhibits Topo I by formation of a covalent DNA-Topoisomerase intermediate.
How does Irinotecan and Topotecan work?
Inhibits Topo I --> inhibits DNA replication and transcription
True or False. Irinotecan is given IV and a dose limiting ADR is life threatening diarrhea.
True or False. Irinotecan is a prodrug
What drugs are topo II inhibitors?
What part(s) of the cell cycle do Topo II inhibitors work on?
S and G2 phase
How do cancer cells begin to resist Topo II inhibitors?
1) Cells overexpressing TOP2--> hypersensitive
2) Cells expressing low levels of TOP2 --> resistant/non-effective
True or False. Etoposide can cause secondary malignancies
True. All topo II inhibitors can cause this from drug induced translocations
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