Exam 3 Cancer MOAs Flashcards
1
Q
Tamoxifen
A
SERM prodrug
2
Q
Raloxifen
A
SERM without endometrial cancer risk
3
Q
Fulvestrant
A
SERD no agonist effects
4
Q
Anastrozole
A
Nonsteroidal aromatase inhibitor
5
Q
Letrozole
A
Nonsteroidal aromatase inhibitor
6
Q
Exemestane
A
Steroidal aromatase inhibitor
7
Q
Medroxyprogesterone acetate
A
protesterone agonist inhibits estrogen dependent proliferation in endometrial cancer
8
Q
Leuprolide
A
GnRH agonist (breast and prostate cancer)
9
Q
Goserelin
A
GnRH agonist (breast and prostate cancer)
10
Q
Abarelix
A
GnRH antagonist
11
Q
Degarelix
A
GnRH antagonist
12
Q
Bicalutamide
A
Androgen antagonist
13
Q
Nilutamide
A
Androgen antagonist
14
Q
Enzalutamide
A
Very potent androgen antagonist
15
Q
Abiraterone
A
Irreversible inhibitor of early hormone synthesis, used for prostate cancer and increases cholesterol
16
Q
Finasteride
A
5-a reductase inhibitor, type II only
17
Q
Dutasteride
A
5-a reductase inhibitor, type I and II
18
Q
Gefitinib
A
Type I EGFR kinase inhibitor
19
Q
Erlotinib
A
Type I EGFR kinase inhibitor
20
Q
Afatinib
A
Covalent EGFR kinase inhibitor
21
Q
Osmeritinib
A
Covalent T790M mutant EGFR kinase inhibitor
22
Q
Lapatinib
A
Reversible inhibitor of EGFR and HER2
23
Q
Sorafenib, axitinib, regorafenib, nitedanib, lenvatinib
A
Inhibit VEGFR
24
Q
Crizotinib
A
Type II inhibitor of cMET (HGF receptor) and ALK fusion kinase
25
Cabozantinib
Type II inhibitor of cMET, RET, and VEGFR2 can overcome some resistance mutations to crizotinib
26
Imatinib
Type II inhibitor of Philadelphia chromosome ABL tyrosine kinase, PDGFR, and c-Kit.
27
Nilotinib
Inhibitor of BCR-Abl (philadelphia chromosome) mutants that are resistant to imatinib
28
Ponatinib
Inhibits all major mutant forms of BCR-Abl including T315I
29
Dasatinib
Inhibits BCR-Abl and Src oncogene
30
Bosutinib
Inhibits BCR-Abl and Src oncogene
31
Sorafenib
General kinase inhibitor (Raf, VEGFR, p38 MAPK), not used much for melanoma due to V600 mutation
32
Vemurafenib
Inhibits V600E mutant B-Raf kinase in MAPK/MEK/ERK pathway, BUT ACTIVATES WILD TYPE
33
Dabrafenib
Inhibits BRAF-V600 kinase, STILL ACTIVATES WILD TYPE
34
Trametinib
ONLY type III allosteric inhibitor, targets MEK1 and MEK2 kinases, inhibits downstream signaling in wild type cells activated by dabrafenib.
35
Idelalisib
Inhibits PI3k lipid kinase!
36
Ibrutinib
Covalent inhibitor of BTK, downstream of B cell receptor
37
Sunitinib
Type II inhibitor of VEGFR
38
Pazopanib
General tyrosine kinase inhibitor
39
Vandetanib
Inhibits VEGFR, EGFR, and RET
40
Sirolimus
Inhibits mTORC1 and mTORC2 serine-threonine kinase to block IL-2 signal transduction
41
Everolimus
Inhibits mTOR1 (only) serine-threonine kinase to block IL-2 signal transduction
42
Trastuzumab
Mab binds HER2/ErbB2, inhibiting function and killing cell
43
Pertuzumab
Binds HER2/ErbB2, inhibits dimerization
44
Cetuximab
Binds EGFR, will not work if KRAS mutation or constitutively active
45
Panitumumab
Binds EGFR, not if KRAS mutation
46
Rituximab
Binds CD20 on B cells
47
Ofatumumab/obinutuzumab
Binds CD20 on B cells
48
Bevacizumab
Binds VEGF LIGAND and prevents blocking to VEGFR
49
Ramucirumab
Binds VEGF RECEPTOR
50
Ado-trastuzumab emtansine
ADC that localizes metransine to HER2 overexpressing cells and has Herceptin function as well
51
Brentuximab vedotin
Binds CD30 on lymphoma cells, releases microtubule inhibitor and causes immune response
52
Ipilimumab
Binds CTLA-4 receptor, reversing inhibition on cytotoxic T cells. Stimulates immune system.
53
Pembrolizumab/Nivolumab
Binds PD1 RECEPTOR on T cells, stopping inhibitory signal and activating T cells.
54
Atezolizumab
Binds PD1 LIGAND on tumor cells and macrophages, stopping inhibition and activating immune system.
55
Blinatumomab
Recombinant protein binds T cell receptor directly to CD19 on B cells, allowing T cell to kill B cell
56
Aldesleukin
IL-2 stimulates inflammation and cell killing
57
Interferon a
Inhibits cell proliferation and enhances immune response
58
Aflibercept
Fusion protein of VEGF receptor plus Fc of IgG sequesters VEGF ligand
59
Romidepsin
Prodrug of HDAC inhibitor, which leads to re-expression of tumor suppressor genes. Can reactivate DNA viruses
60
Vorinostat
HDAC inhibitor re-expresses tumor suppressor genes, can reactivate DNA viruses
61
Belinostat
HDAC inhibitor re-expresses tumor suppressor genes, can reactivate DNA viruses
62
Azacytidine
Incorporates into DNA and covalently binds DNMT enzyme, reactivates tumor suppressor genes.
63
Decitabine
DNMT inhibitor reactivates tumor suppressor genes
64
Tretinoin
Binds retinoic acid receptor to inhibit proliferation and induce differentiation
65
Bexarotene
Retinoid agonist for retinoid receptor, vit D receptor, PPAR, and thyroid receptor. Induces differentiation
66
Thalidomide (pomalidomide, lenalidomide)
Blocks bFGF and VEGF effects
67
Bortezomib
Reversible proteasome inhibitor
68
Carfilzomib
Irreversible proteasome inhibitor, NO neuropathy
69
Vismodegib/sonidegib
Inhibit smoothened from activating GLI1 in Hedgehog pathway for basal cell carcinoma
70
Venetoclax
Inhibits protein-protein interaction for BCL-2, a protein that prevents apoptotic proteins from working.
71
Omacetaxine
Inhibits protein translation at ribosome
72
Asparaginase
Degrades circulating asparagine, starving cancer cells that are deficient in asparagine synthetase
73
Denosumab
Mimics osteoprotegrin, binds RANKL prevents from inducing osteoclast proliferation
74
Allopurinol
inhibits xanthine oxidase, preventing buildup of uric acid and tumor lysis syndrome
75
Rasburicase
Enzyme that breaks down uric acid preventing tumor lysis syndrome
76
Filgrastim
G-CSF promotes granulocyte production (neutropenia)
77
Sargramostim
GM-CSF promotes granulocyte progenitor production (more broad stimulation of granulocytes)
78
Oprelvekin
Increases platelet production
79
Epoetin
Stimulates RBC production
80
Olaparib
PARP inhibitor stops repair of DNA in cells with BRCA mutation
81
Palobociclib
Cdk4/6 kinase inhibitor blocks progression of tumor from G1-S phase, reducing proliferation
82
Mustine
Old nitrogen mustard DNA alkylating agent
83
Bendamustine
Nitrogen mustard with better tolerability, only partial cross resistance to other alkylating agents
84
Chlorambucil
Nitrogen mustard alkylating agent
85
Melphalan
Nitrogen mustard alkylating agent
86
Cyclophosphamide
Prodrug nitrogen mustard alkylating agent converted to active form within tumor cell. Less bone marow toxicity d/t elevated ALDH in bone marrow cells. Hemorrhagic cystitis
87
Ifosfamide
Prodrug nitrogen mustard with hemorrhagic cystitis, increased CNS toxicity over cyclophos
88
Mesna
Thiol that accumulates in urine to neutralize toxic cyclophosphamide metabolites
89
Carmustine
Nitrosurea alkylating agent converted to diazonium ion within tumor cell, penetrates BBB
90
Lomustine
Nitrosurea alkylating agent converted to diazonium ion within tumor cell, penetrates BBB
91
Busulfan
Alkyl sulfonate alkylating agent, "busulfan lung"
92
Dacarbazine
Monoalkylating agent blocks replication enzyme function via creation of methyldiazonium ion
93
Temozolomide
Becomes methyldiazonium without liver activation, alkylates DNA and inhibits replication. Crosses BBB!
94
Cisplatin
Platinum compound forms intrastrand DNA crosslinks, active aquo form favored within cell. Dose-limiting NEPHROTOXICITY, minimal myelosuppression
95
Carboplatin
Platinum compound forms intrastrand DNA crosslinks, active aquo formed slowly within cell. SIGNIFICANT MYELOSUPPRESSION, minimal nephrotoxicity
96
Oxaliplatin
Platinum DNA intrastrand crosslinker, dose-limiting SENSORY NEUROPATHY, minimal nephrotoxicity
97
Mitomycin C
Aziridine-containing product similar to nitrogen mustard, forms monoadducts and crosslinks. MYELOSUPPRESSION
98
Radium 223 dichloride
Absorbed into bone, radiates bone metastasis
99
Procarbazine
Somehow inhibits DNA, RNA, and protein synthesis, not cross resistant with alkylating agents.
100
5-fluorouracil
Covalently binds to thymidylate synthase and causes thymineless death. Also incorporated into RNA and interferes with function. Leucovorate and thymidine pre-treatment increase efficacy.
DPD polymorphism causes life threatening toxicity
101
Fluorodeoxyuridine
Deoxyribonucleoside 5-FU inhibits thymidine synthesis
102
Capecitabine
Orally active prodrug of 5-FU, activated in liver, tissue, and tumor
103
Cyrosine arabinoside
Nucleoside with arabinose sugar, competitively inhibits DNA polymerase, incorporated into DNA and inhibits polymerization.
104
Gemcitabine
Nucleoside analog is incorpotated into DNA but HALTS chain elongation.
105
6-mercaptopurine
Inhibits multiple enzymes in purine synthesis pathway (adenine and guanine). Activated by HGPRT.
Inactivated by TPMT - POLYMORPHISM
Allopurinol increases toxicity
106
6-thioguanine
Thio analog of guanine, similar activity to 6-MP (cross resistance).
TMPT polymorphism!
NO interaction with allopurinol
107
Fludarabine/nelarabine/cladribine
Arabinose adenosine analog inhibits DNA polymerase and ribonucleotide reducatase -- DNA replication and transcription. Activity against cycling and resting cells.
108
Methotrexate
Inhibits dihydrofolate reductase, enzyme that activates dietary folate. Inhibits S phase
109
Pralatrexate
Inhibits DHFR selectively in cells with RFC-1 transporter (certain cancers), inhibits S phase.
110
Pemetrexed
Inhibits DHFR, thymidylate synthase, and glycinamide ribonucleotide formyltransferase, so decreased risk of drug resistance. Inhibits S phase.
111
Leucovorin
Reverses effects of DHFR inhibition
112
Hydroxyurea
Decreases production of deoxyribonucleotides (DNA synthesis) - S phase
113
Actinomycin C
Binds DNA, inhibits transcription and replication. Non cell cycle specific
114
Irinotecan
Intercalates with DNA, inhibits topoisomerase I. S phase selective.
UGT1A1 increases risk of toxicity
115
Topotecan
Topoisomerase I inhibitor
116
Daunorubicin
Anthracycline Topoisomerase II inhibitor causes DS DNA breaks and free radical damage. Non-cell cycle dependent (but G2/M more selective). CARDIOTOXICITY
117
Doxorubicin
Anthracycline topo II inhibitor. CARDIOTOXICITY, severe extravasation reaction. Not cell cycle dependent.
118
Epirubicin
Anthracycline topo II inhibitor. Faster elimination, so less cardiotoxicity. Not cell cycle dependent.
119
Idarubicin
Lipophilic anthracycline topo II inhibitor. Cardiotoxicity. Not cell cycle dependent.
120
Dexrazoxane
Analog of EDTA binds iron, blocks free radical-induced cardiotoxicity of anthracycline topo II inhibitors
121
Mitoxantrone
Topoisomerase II inhibitor without free radical formation -- NO/minimal cardiotoxicity
122
Etoposide/teniposide
Epipodophyllotoxin inhibitor of topoisomerase II that does not intercalate DNA. Better for cardiac function. G2/M CELL CYCLE SPECIFIC
123
Bleomycin
Intercalates into DNA, causes free radical induced breaks in DNA. PULMONARY toxicity is dose-limiting and cumulative.
124
Vincristine
Inhibits microtubule assembly. Dose-limiting NEUROTOXICITY, severe extravasation reaction. M phase specific.
125
Vinblastine
Inhibits microtubule assembly. Dose-limiting MYELOSUPPRESSION, less severe neurotoxicity. M phase specific.
126
Vinorelbine
Inhibits microtubule assembly. Dose-limiting MYELOSUPPRESSION, mild neurotoxicity. M phase specific.
127
Eribulin
Prevents elongation at microtubule ends. Low rate of neurotoxicity.
128
Paclitaxel
Blocks depolymerization and segregation of sister chromatids, leading to mitotic arrest. M phase specific. Dose-limiting MYELOSUPPRESSION.
129
Docetaxel
Blocks depolymerization and segregation of sister chromatids, leading to mitotic arrest. M phase specific. Dose-limiting MYELOSUPPRESSION.
130
Cabazitaxel
Blocks depolymerization and segregation of sister chromatids, leading to mitotic arrest. M phase specific. Dose-limiting MYELOSUPPRESSION. ONLY taxel that is not a Pgp substrate.
131
Epothilone/ixabepilone
Promotes tubulin polymerization, stabilizes microtubules. More potent than taxols, not cross resistant. Neurotoxicity common but reversible.
