L topo/microtubule Flashcards
Cells in __ phase are most sensitive to topo 1 induced cleavage *
S
thing highlighted red under drug resistance for topo 1 inhibitors *
glutathione s-transferase overexpression
T or F:
Topotecan and Irinotecan are water soluble
True
Topotecan class
topo 1 inhibitor
Irinotecan class
topo 1 inhbitor
dose limiting toxicity thing of irinotecan (not symptom)
UGT1A1
Topoisomerase I inhibitors primarily halt cells in which phase of the cell cycle?
A. G0/G1
B. S
C. G2
D. M
B
Many compounds inhibit topo II, but only ones that produce what are cancer therapies
double stranded DNA breaks, (does this not just make sense for everything)
Main topo II inhibitor in class
Doxorubicin
Example of anthracyclines (topo II inhibitors) (just try)
doxorubicin
daunorubicin
epirubicin
idarubicin
T or F:
Since topo II inhibitors act as intercalators, they are much less toxic than other therapies
False, more toxicity
T or F:
Topo II inhibitors release free radicals that can cause dna damage
true, one of the more important aspects of the classs
what do the free radicals from topo II inhibitors do to us that is highlighted red and super important? *
cause cardiotoxicity since heart tissue ahs low levels of enzymes that neutralize free radicals
T or F:
Topo II inhibitors act during G2/M and are cell cycle dependent
False, they do have activity there but they are considered non-cell cycle dependent
What is another toxicity that doxorubicin has that isnt cardio related? (also highlighted in red) *
severe local tissue damage if extravasated
what drug is given in combo with doxorubicin to mediate toxicity (specifically cardio) *
dexrazoxane
Cardiotoxicity of doxorubicin is believed to be caused by what?
iron-catalyzed free radical formation
What class is etoposide?
Topo II inhibitor
Cell cycle stage specificity of etoposide***
G2
T or F:
Etoposide inhibits re-ligation of double strand breaks induced by topo II and intercalates like doxorubicin
false. it does not intercalate **
2 pumps that contribute to resistance of topo II inhibitors.
pGp and MRP
bleomycin target(s)
Imidazole –
free radical
Thiazole -
intercalator
Bleomycin has its greatest effect on cells in the __ and __ phases of the cell cycle
G2 and M
dose-limiting toxicity related to bleomycin
pulmonary (think blow)
bleomycin is inactivated by bleomycin aminohydrolase, which is in high concentrations everywhere but _____ and _____
skin and lung
T or F:
bleomycin has rash side effects
true
Prevent microtubule assembly:
A. Vinca alkaloids
B. Taxanes
A. Vinca alkaloids
Prevent microtubule disassembly:
A. Vinca alkaloids
B. Taxanes
B. Taxanes
T or F:
Cells treated with vinca alkaloids cannot build up any microtubules
True
T or F:
taxanes stabilize microtubules
true
T or F:
Taxanes stabilizing microtubules is good because we want cellular stability
false, dynamic instability is important for microtubules to find their chromosomes
T or F:
vinca alkaloids destabilize microtubules
true
T or F:
vinca alkaloids are small molecules that get into cells with ease
false, large, need specific transporter
what do vinca alkaloids bind to?
tubulin
vinca alkaloids binding to tubulin leads to no attachment of microtubules to the _______ which is called what?
spindles
mitotic arrest
microtubules are critical to nerve cell axon function, therefore a toxicity of vinca alkaloids would be what?
peripheral neuropathy / neurotoxicity
Vincristine 2 main things listed under toxicity
extravasation causes severe inflammation
neurotoxicity *
T or F:
The neurotoxicity from vinca alkaloids is dose dependent
true
Eribulin is a what inhibitor
microtubule polymerization inhibitor
T or F:
Eribulin has a lower rate of toxicity than other microtubule inhibitor drugs *
true
What does Paclitaxel do to microtubules?
stabilizes tf outta them bitches
what do the taxane drugs end with?
-taxl
what do taxanes bind to?
tubulin
what is the main thing that leads to mitotic arrest when discussing taxanes?
stabilizing the microtubules -> block depolymerization and segregation of sister chromatids
Paclitaxel dose limiting toxicity thing
myelosuppression
what is paclitaxel linked to to increase solubility and circulation time of the drug
albumin
Wtf is an epothilone (ixabepilone) and what does does it bind to / do
binds to tubulin
promotes tubulin polymerization and microtubule stabilization
T or F:
Epothilones (ixabepilone) are not cross-resistant with taxanes
True
T or F:
Epothilones (ixabepilone) is a poor PGP substrate
true
Which of the following microtubule inhibitors block the polymerization of tubulin?
A. Paclitaxel
B. Vincristine
C. Ixabepilone
B
