study guide Flashcards
5-fluorouracil (5-FU):
Target:
Class:
CC phase:
DL SE:
thymidylate synthase
antimetabolite (uridine analog)
S
myelosuppression
5-FU rescue
thymidine
5-FU drug synergy
Leucovorate
5-FU unique resistance mechanism
downregulation of enzyme that convert 5-FU to F-dUMP
increase thymidylate synthase
5-FU genetic testing
5% of pop has polymorphism that results in deficiency of DPD
Cytarabine (Ara-C)
Target:
Class:
CC phase:
DL SE:
- Comp inh of DNA polymerase alpha
- antimetabolite (cytosine analog)
- S phase
- myelosuppression
Cytarabine (Ara-C) synergy
tetrahydrouridine (cytidine deaminase inhibitor)
Cytarabine (Ara-C) resistance mechanisms
downregulation of enzymes that upregulate cytidine deaminase
downregulation of influx transporters
6-Mercaptopurine (6-MP)
Target:
Class:
CC phase:
DL SE:
- multiple enzymes in de novo purine synthesis (blocks synth of purine nucleotides)
- antimetabolite (purine analog, thio-analog of adenine)
- S
- myelosuppression, hematologic toxicity
what drug increases 6-MP toxicity?
allopurinol
unique mechanisms resistance 6-MP
loss of HGPRT (activating enzyme)
6-MP genetic testing
TPMT polymorphism loss of function
methotrexate
Target:
Class:
CC phase:
DL SE:
- DHFR inhibitor
- antifolate
- S
- myelosuppression
methotrexate rescue
Leucovorin
methotrexate resistance mechanism
amplification of DHFR or resistant mutation of DHFR
decreased polyglutamation
Chlorambucil
Target:
Class:
CC phase:
DL SE:
- dna crosslinker
- alkylator
- all phases
- myelosuppression, carcinogenic, teratogenic
unique resistance mechanisms chlorambucil
increase glutathione
increased GST
second malignancies
all antimetabolites/antifolates work in which phase of cell cycle
s
T or F:
all alkylators have risk of second malignancies
true
cyclophosphamide:
Target:
Class:
CC phase:
DL SE:
- DNA crosslinker
- alkylator (prodrug)
- all phases
- hemorrhagic cystitis
what do you give if cyclophosphamide causes hemorrhagic cystitis
mesna
Mitomycin C
Target:
Class:
CC phase:
DL SE:
- bifunctional adducts on DNA
- alkylator (aziridine)
- all phases
- myelosuppression
Cisplatin
Target:
Class:
CC phase:
DL SE:
- covalent crosslinkers of G and A causing strand breaks (forms intrastrands)
- platinum compound
- all phases
- bone marrow, nephrotoxicity (proximal tubule)
T or F:
Cisplatin has a risk of second malignancies
true
irinotecan
Target:
Class:
CC phase:
DL SE:
- topo I
- topo I inhibitor
- S phase
- UGT1A1 polymorphism
irinotecan unique resistance mechanisms
PGP overexpression
MRP overexpression
Glutathione-S-Transferase overexpression*
Topoisomerase downregulation or mutation to prevent inhibitor binding
Doxorubicin:
Target:
Class:
CC phase:
DL SE:
- topo II (intercalates and inhibits double strand re-ligation)
- topo II inhibitor
- Non-specific but greater G2/M activity
- cardiotoxicity bc of free radical damage, also tissue damage with extravasation
what drug prevents doxorubicin cardiotoxicity
dexrazoxane
unique resistance mechanism doxorubicin
glutathione-s-transferase overexpression
bleomycin
Target:
Class:
CC phase:
DL SE:
- imadazole -> free radical, thiazole -> intercalator
- dual mechanism cytotoxic agent (topo/micro)
- G2/M
- pulmonary (blow/bleo)
vincristine
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule assembly (tubule polymerization) and microtubule shortening
- Vinca alkaloid (microtubule destabilizer)
- M
- Neurotoxicity, peripheral neuropathy, myelosuppression rarely significant
Eribulin
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule assembly/elongation
- microtubule destabilizer
- M
- lower neurotoxicity than vinca
Paclitaxel
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule assembly (depolymerization)
- taxane -> microtubule stabilizer
- M
- myelosuppression, neurotoxicity is reversible
Paclitaxel unique resistance mechanism
PgP substrate (except for cabazitaxel)
tubulin mutations
Ixabepilone
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule disassembly (depolymerization)
- microtubule stabilizer (epothilone B analog)
- M
- reversible myelosuppression
Ixabepilone (is/is not) cross-resistant to taxanes
is not
T or F:
Ixabepilone is a poor PgP substrate
true
Enzalutamide
Target:
Class:
CC phase:
DL SE:
- androgen receptor
- full AR antagonist
- not cell cycle specific
- none listed
enzalutamide unique resistance mechanism
AR mutations that result in castration resistant prostate cancer (CRPC)
Abiraterone
Target:
Class:
CC phase:
DL SE:
- 17-a-hydrolase and C17,20 lyase
- steroid analog
- not cell cycle
- increased cholesterol
tamoxifen
Target:
Class:
CC phase:
DL SE:
- ER
- SERM
- not cell cycle specific
- hot flashes, increased risk of endometrial cancer