study guide Flashcards
1
Q
5-fluorouracil (5-FU):
Target:
Class:
CC phase:
DL SE:
A
thymidylate synthase
antimetabolite (uridine analog)
S
myelosuppression
2
Q
5-FU rescue
A
thymidine
3
Q
5-FU drug synergy
A
Leucovorate
4
Q
5-FU unique resistance mechanism
A
downregulation of enzyme that convert 5-FU to F-dUMP
increase thymidylate synthase
5
Q
5-FU genetic testing
A
5% of pop has polymorphism that results in deficiency of DPD
6
Q
Cytarabine (Ara-C)
Target:
Class:
CC phase:
DL SE:
A
- Comp inh of DNA polymerase alpha
- antimetabolite (cytosine analog)
- S phase
- myelosuppression
7
Q
Cytarabine (Ara-C) synergy
A
tetrahydrouridine (cytidine deaminase inhibitor)
8
Q
Cytarabine (Ara-C) resistance mechanisms
A
downregulation of enzymes that upregulate cytidine deaminase
downregulation of influx transporters
9
Q
6-Mercaptopurine (6-MP)
Target:
Class:
CC phase:
DL SE:
A
- multiple enzymes in de novo purine synthesis (blocks synth of purine nucleotides)
- antimetabolite (purine analog, thio-analog of adenine)
- S
- myelosuppression, hematologic toxicity
10
Q
what drug increases 6-MP toxicity?
A
allopurinol
11
Q
unique mechanisms resistance 6-MP
A
loss of HGPRT (activating enzyme)
12
Q
6-MP genetic testing
A
TPMT polymorphism loss of function
13
Q
methotrexate
Target:
Class:
CC phase:
DL SE:
A
- DHFR inhibitor
- antifolate
- S
- myelosuppression
14
Q
methotrexate rescue
A
Leucovorin
15
Q
methotrexate resistance mechanism
A
amplification of DHFR or resistant mutation of DHFR
decreased polyglutamation
16
Q
Chlorambucil
Target:
Class:
CC phase:
DL SE:
A
- dna crosslinker
- alkylator
- all phases
- myelosuppression, carcinogenic, teratogenic
17
Q
unique resistance mechanisms chlorambucil
A
increase glutathione
increased GST
second malignancies
18
Q
all antimetabolites/antifolates work in which phase of cell cycle
A
s
19
Q
T or F:
all alkylators have risk of second malignancies
A
true
20
Q
cyclophosphamide:
Target:
Class:
CC phase:
DL SE:
A
- DNA crosslinker
- alkylator (prodrug)
- all phases
- hemorrhagic cystitis
21
Q
what do you give if cyclophosphamide causes hemorrhagic cystitis
A
mesna
22
Q
Mitomycin C
Target:
Class:
CC phase:
DL SE:
A
- bifunctional adducts on DNA
- alkylator (aziridine)
- all phases
- myelosuppression
23
Q
Cisplatin
Target:
Class:
CC phase:
DL SE:
A
- covalent crosslinkers of G and A causing strand breaks (forms intrastrands)
- platinum compound
- all phases
- bone marrow, nephrotoxicity (proximal tubule)
24
Q
T or F:
Cisplatin has a risk of second malignancies
A
true
25
irinotecan
Target:
Class:
CC phase:
DL SE:
- topo I
- topo I inhibitor
- S phase
- UGT1A1 polymorphism
26
irinotecan unique resistance mechanisms
PGP overexpression
MRP overexpression
Glutathione-S-Transferase overexpression*
Topoisomerase downregulation or mutation to prevent inhibitor binding
27
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
28
what drug prevents doxorubicin cardiotoxicity
dexrazoxane
29
unique resistance mechanism doxorubicin
glutathione-s-transferase overexpression
30
bleomycin
Target:
Class:
CC phase:
DL SE:
- imadazole -> free radical, thiazole -> intercalator
- dual mechanism cytotoxic agent (topo/micro)
- G2/M
- pulmonary (blow/bleo)
31
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
32
Eribulin
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule assembly/elongation
- microtubule destabilizer
- M
- lower neurotoxicity than vinca
33
Paclitaxel
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule assembly (depolymerization)
- taxane -> microtubule stabilizer
- M
- myelosuppression, neurotoxicity is reversible
34
Paclitaxel unique resistance mechanism
PgP substrate (except for cabazitaxel)
tubulin mutations
35
Ixabepilone
Target:
Class:
CC phase:
DL SE:
- tubulin -> inhibition of microtubule disassembly (depolymerization)
- microtubule stabilizer (epothilone B analog)
- M
- reversible myelosuppression
36
Ixabepilone (is/is not) cross-resistant to taxanes
is not
37
T or F:
Ixabepilone is a poor PgP substrate
true
38
Enzalutamide
Target:
Class:
CC phase:
DL SE:
- androgen receptor
- full AR antagonist
- not cell cycle specific
- none listed
39
enzalutamide unique resistance mechanism
AR mutations that result in castration resistant prostate cancer (CRPC)
40
Abiraterone
Target:
Class:
CC phase:
DL SE:
- 17-a-hydrolase and C17,20 lyase
- steroid analog
- not cell cycle
- increased cholesterol
41
tamoxifen
Target:
Class:
CC phase:
DL SE:
- ER
- SERM
- not cell cycle specific
- hot flashes, increased risk of endometrial cancer
41
fulvestrant
Target:
Class:
CC phase:
DL SE:
- ER
- SERD (antagonist only)
- not cell cycle specific
- n/a
42
tamoxifen random drug interaction thing
BC prophylaxis
42
Predinisolone
Target:
Class:
CC phase:
DL SE:
- no target listed?
- corticosteroid
- no cell cycle phase
- no important SE
43
Letrozole
Target:
Class:
CC phase:
DL SE:
- aromatase
- non-steroidal comp aromatase inhibitor
- no cell cycle phase shit
- bone density loss/ fracture
43
Exemestane
Target:
Class:
CC phase:
DL SE:
- aromatase
- steroidal aromatase inhibitor (suicide inhibitor/irreversible)
- no cell cycle shit here
- hot flashes, edema, weight gain, increased cholesterol *
44
Leuprolide
Target:
Class:
CC phase:
DL SE:
- GnRH receptor
- GnRH analog
- no phase
- "flare effects", hot flashes, sexual dysfxn, gynecomastia
45
Imatinib
Target:
Class:
CC phase:
DL SE:
- BCR-Abl TK
- type II small molecule Bcr-Abl inhibitor
- no phase
- N/V, fluid retention, neutropenia, thrombocytopenia
46
Imatinib genetic testing
philadelphia chromosome
47
Ponatinib
Target:
Class:
CC phase:
DL SE:
- Bcr-Abl
- Bcr-Abl inhibitor
- no cell cycle shit
- no important SE
48
Midostaurin:
Target:
Class:
CC phase:
DL SE:
- fms-like TK 3 (FLT3) in AML
- 1st gen FLT3 inhibitor
- no phase
- no crazy SEe
49
Creneolanib
Target:
Class:
CC phase:
DL SE:
- fms-like TK 3 (FLT3)
- 2nd gen FLT3 inhibitor for AML
- no cell cycle shit
- no se listed
50
Quizartinib
Target:
Class:
CC phase:
DL SE:
- FLT3
- type II FLT3 inhibitor
- no cell cycle shit
- no listed SE
51
Quizartinib genetic testing thing *
specific for internal tandem duplication (ITD) mutations
52
Sirolimus
Target:
Class:
CC phase:
DL SE:
- mTOR (mammalian target of Rapamycin)
- Rapamycin analogs
- no cell cycle
53
sirolimus random drug interaction thing
inhibits immune response by blocking IL-2 signaling transduction
54
Alectinib
Target:
Class:
CC phase:
DL SE:
- anaplastic TK (ALK)
- ALK inhibitor
- no cell cycle shit
- no crazy SE
55
Alectinib genetic testing thing *
Fusion gene of ALK to ELM4
56
Dabrafenib
Target:
Class:
CC phase:
DL SE:
- BRAF-V600
- 2nd gen BRAF inhibitor
- no cell cycle
- no listed SEs
57
Dabrafenib is paired with what other drug for BRAF-V600 mutant metastatic melanoma
trametinib
58
Genetic testing thing for dabrafenib
BRAF-V600 mutationt
59
Trametinib
Target:
Class:
CC phase:
DL SE:
- MEK1 and MEK2
- type III allosteric MEK inhibitor
- no cell cycle shit
- RASH, diarrhea, lymphedema
60
Acalabrutinib
Target:
Class:
CC phase:
DL SE:
- Brutons TK (BTK)
- 2nd gen covalent BTK inhibitor
- no cell cycle shit
- no listed SE
61
Afatinib
Target:
Class:
CC phase:
DL SE:
- Covalent inhibitor of al ErBb receptors
- EGFR inhibitor
- no cell cycle
- rash
62
Afatinib genetic testing stuff
QIAGEN for detection of exon 19 or 21 deletions/mutations
63
gefitinib
Target:
Class:
CC phase:
DL SE:
- EGFR TK
- 1st gen reversible EGFR inhibitor
- no cell cycle
- fatigue, RASH, diarrhea
64
what mutation causes resistance to gefitinib
T790M
65
genetic testing gefitinib
exon 19 or 21 mutations
66
osimertinib
Target:
Class:
CC phase:
DL SE:
- EGFR TK
- 3rd gen covalent EGFR inhibitor
- no cell cycle
- rash i think
67
Osimertinib genetic testing and fun fact thing
t790M mutation, it is effective for this
68
Lapatinib
Target:
Class:
CC phase:
DL SE:
- EGFR and HER2
- EGFR and HER2 reversible inhibitor, it is a small molecule TKI
- no cell cycle shit
- diarrhea, N/V, reversible decrease in cardiotoxicity
69
Lapatinib is commonly combined with what for metastatic breast cancer
capecitabine
70
Tucatinib
Target:
Class:
CC phase:
DL SE:
- HER2
- TK1 HER2 inhibitor
- no cell cycle
- reduced SE's compared to lapatinib or covalent pan-ErBb inhibitors
71
Tucatinib genetic testing
HER2+ breast cancer
72
Trastuzumab is combined with what
Pertuzumab
73
Trastuzumab/Pertuzumab
Target:
Class:
CC phase:
DL SE:
- HER2
- Recombinant humanized mAB
- no cell cycle
- flu-like sxs, cardiomyopathy
74
what does pertuzumab do that is an important reason it is combined with trastuzumab?
it has different binding sites on HER2 and inhibits dimerization
75
Cetuximab
Target:
Class:
CC phase:
DL SE:
- EGFR completely inhibits binding of EGF and TGF-alpha
- Recombinant chimeric mAB, fully humanized
- no cell cycle
- severe infusion reaction, rash, fever
76
bevacizumab
Target:
Class:
CC phase:
DL SE:
- VEGF (ligand), blocks interaction with endothelial receptors
- recombinant humanized mAB
- no cell cycle
- no listed SE's
77
bevacizumab is used in combo with ______ for 1st line tx of metastatic colorectal cancer
5-FU, this drug has no efficacy as a single agent
78
Ramucirumab
Target:
Class:
CC phase:
DL SE:
- VEGF receptor
- recombinant humanized mAB
- no cell cycle
- used in combo with 5-FU
79
Rituximab
*Target:
Class:
CC phase:
DL SE:
- CD20 in normal B lymphocytes and immature pre B cells
- not sure rn but mAB
- no cell cycle
- no se listed
80
Daratumumab
*Target:
Class:
CC phase:
DL SE:
- CD38 on plasma B cells
- mAB
- none
- none listed
81
*Ipilimumab
Target:
Class:
CC phase:
DL SE:
- CTLA-4 receptor -> reverses cytotoxic T lymphocyte inhibition
- recombinant human mAB
- none
- severe immune-mediated adverse effects (inflammatory) (may require steroids)
82
Pembrolizumab
Target:
Class:
CC phase:
DL SE:
- Binds PD-1 receptor expressed on T cells
- mAB
- none
- none listed
83
pembrolizumab genetic testing
PDL1 test for tx of NSCLC
84
Atezolizumab
Target:
Class:
CC phase:
DL SE:
- Binds PDL-1 Receptor
- PDL-1 mAB
- none
- none listed
85
Trastuzumab Emtansine
Target:
Class:
CC phase:
DL SE:
- HER2/Neu receptor, emtansine inhibits microtubule assembly
- ADC, emtansine is cytotoxic
- none
- trastuzumab SE's, emtansine gives thrombocytopenia and hepatotoxicity
86
Trastuzumab Derutexan
Target:
Class:
CC phase:
DL SE:
- HER2/Neu receptor, topo I
- ADC + topo I inhibitor
- none
- trastuzumab effects
87
Blinatumomab
Target:
Class:
CC phase:
DL SE:
- binds CD3 and brings activated T-cell into proximity of CD19
- BiTE
- none
- cytokine release syndrome
88
Mosunetuzumab
Target:
Class:
CC phase:
DL SE:
- CD3 and CD20
- BiTE
- none
- same as other BiTES
89
Teclistamab
Target:
Class:
CC phase:
DL SE:
- CD3 on T-cells and B-cell maturation antigen, BCMA of multiple myeloma cells
- BiTE
- none
- same as other BiTE
90
Taquetamab
Target:
Class:
CC phase:
DL SE:
- CD3, GPRC5D
- BiTE
- none
- other BiTEs
91
Sipuleucel-T
Target:
Class:
CC phase:
DL SE:
- antigen presenting cells activated by ex vivo with PAP-GM-CSF
- PAP-GM-CSF
- none
- flu like sxs, increased risk of stroke
92
CAR-T
Target:
Class:
CC phase:
DL SE:
- T cell activation using CD19 as target
- chimeric antigen receptor T cells (CAR-T) duh
- none
- none listed
93
Olaparib:
Target:
Class:
CC phase:
DL SE:
- PARP to trap to DNA
- PARP inhibitor
- none
- no crazy ones listed
94
think of what fun 2 word thing when you see olaparib
synthetic lethality
95
Palbociclib
Target:
Class:
CC phase:
DL SE:
- CDK4/6
- Kinase inhibitor -> targets kinases directly involved in cell cycle control
- G1
- neutropenia, nausea, fatigue, diarrhea, vomiting
96
Palbociclib genetic testing
BRCA1/2
97
Bortemzomib
Target:
Class:
CC phase:
DL SE:
- 26S proteasome
- proteasome inhibitor
- none
- none listed that are special
98
5-azacytidine
Target:
Class:
CC phase:
DL SE:
- RNA
- DNMT inhibitor
- none
- none listed
99
Venetoclax:
Target:
Class:
CC phase:
DL SE:
- BCL-2, anti apoptotic protein
- BCL-2 inhibitor
- none
- none listed
100
Venetoclax combined with what for AML
azacitidine
101
Pomalidomide
Target:
Class:
CC phase:
DL SE:
- IKZF TFs
- Thalidomide analog
- none
- none listed
