Topoisomerase Inhibitors and Microtubule Inhibitors Flashcards
Where in the cell cycle do Topo1 inhibitors work?
S phase (Irinotecan)
Where in the cell cycle do Topo2 inhibitors work?
G2 (Etoposide, Bleomycin)
non-cell cycle specific (Doxorubicin)
What is the mechanism of action of Topoisomerase Type 1 inhibitors?
-after single strand break, stays stuck to DNA strand and prevents religation, causes physical block to DNA replication and transcription
What is the mechanism of action of Topoisomerase Type 2 inhibitors?
What are the Topo1 inhibitors?
Irinotecan (SN-38), topotecan
What polymorphism is seen that affects patients on Irinotecan?
~10% has increased toxicity due to low expression of UGT1A1
What are the Topo2 inhibitors?
Doxorubicin, Etoposide
What can help mediate the toxicity with Doxorubicin?
Dexrazoxane, Etoposide
-binds to iron and neutralizes free radicals
What is the mechanism of action for Bleomycin?
-intercalates, single & ds breaks via radical intermediate
What phase in the cell cycle is the microtubule inhibitors?
M phase
What are the microtubule disassembly inhibitors/microtubule stabilizers?
Taxanes
What are the microtubule assembly inhibitors/microtubule destabilizers?
Vinca alkaloids
What are the Vinca alkaloid medications?
Vincristine, Eribulin
What is the dose-limiting side effect of vincristine
neurotoxicity
-peripheral neurotoxicity
What is the mechanism of action of Vincristine?
inhibits polymerization (microtubule assembly)
