Oncology (Dykhuizen & Mabe)

Question 1

What are the antimetabolites/Antifolates?

Answer 1

5-Fu, cytarabine, 6-MP, methotrexate

Question 2

5-Fu info

Answer 2

antimetabolite; inhibits thymidine synthesis from uracil; S-Phase; thymidine = “antidote”
leucovorin = synergy

Question 3

Cytarabine (Ara-C)

Answer 3

antimetabolite; cytosine analog; competitive inhibitor of DNA polymerase-a, S-Phase, tetrahydrouridine = synergy

Question 4

6-MP

Answer 4

purine analog: blocks the synthesis of purine nucleotides S-Phase “allopurinol: blocks xanthine oxidase from
breaking down 6-MP & can lead to 6-MP toxicity” loss of HGPRT, the activating enzyme deficiency of TPMT increase risk of 6-MP toxicity

Question 5

methotrexate

Answer 5

antifolate
DHFR inhibition reduces FH4 & inhibits TMP synthesis (inhibits RNA and protein synthesis) (also inhibits purine and pyrimidine base synthesis) S-Phase leucovorin = “antidote” “Amplification of DHFR gene or mutation to resistant form
Decreased polyglutamation results in decreased intracellular MTX”

Question 6

Chlorambucil

Answer 6

non-phase specific alykator

Question 7

cyclophosphamide

Answer 7

prodrug alkylator

Question 8

mitomycin-c

Answer 8

alkylator

Question 9

cisplatin

Answer 9

platinum compound; intrastrand cross-links

Question 10

topo I inhibitor

Answer 10

ironotecan, topotecan

Question 11

topotecan

Answer 11

topo-I inhibitor

Question 12

doxorubicin

Answer 12

topo-II inhibitor and intercalator

Question 13

etoposide

Answer 13

topo-II inhibitor

Question 14

vincristine

Answer 14

microtubule inhibitor

Question 15

Bleomycin

Answer 15

topo-II inhibitor and intercalator

Question 16

erubulin

Answer 16

microtubule inhibitor

Question 17

paclitaxel

Answer 17

microtubule stabilizer

Question 18

ixabepilone

Answer 18

microtubule stabilizer

Question 19

enzalutamide

Answer 19

high affinity and binds to AR

Question 20

abiraterone

Answer 20

CYP17 inhibitor

Question 21

tamoxifen

Answer 21

SERM; raloxifene also in class

Question 22

fulvestrant

Answer 22

SERD

Question 23

letrozole, anastrozole

Answer 23

non-steroidal aromatase inhibitor

Question 24

exemastene

Answer 24

steroidal aromatase inhibitor

Question 25

leuprolide

Answer 25

GnRH analog

Question 26

imatinib

Answer 26

type II small molecule inhibitor of Abl tyrosine kinase

Question 27

ponatinib

Answer 27

type II small molecule inhibitor of Abl tyrosine kinase effective against T315I mutation-- effective against all major BCR-ABL mutations

Question 28

midostaurin

Answer 28

first gen FLT3 inhibitor: broad kinase inhibitor

Question 29

quizartinib

Answer 29

Type II FLT3 inhibitor: specific for ITD mutations

Question 30

Crenolanib

Answer 30

second gen FLT3 inhibitor: specific kinase inhibitor

Question 31

sirolimus

Answer 31

inhibit the funciton of mTOR (serine-threonine kinase)

Question 32

alectinib

Answer 32

ALK inhibitor

Question 33

dabrafinib

Answer 33

inhibits BRAF-v600 to treat metastatic melanoma (used in combo with trametinib)

Question 34

trametinib

Answer 34

inhibits MEK1 and MEK2 kinase activity though type III allosteric inhibition (downstream of MET receptor tyrosine kinase)

Question 35

acalabrutinib

Answer 35

second gen covalent BTK (Bruton's Tyrosine Kinase) inhibitor

Question 36

Gefitinib

Answer 36

EGFR tyrosine kinase inhibitor; type I TKI

Question 37

Lapatinib

Answer 37

small molecule TKI, reversible inhibitor of EGFR & HER2

Question 38

afatinib

Answer 38

covalent inhibitor of all ErbB receptors (used for EGFR mutations)

Question 39

Tucatanib

Answer 39

selective HER2 inhibitor

Question 40

Osimertinib

Answer 40

covalent EGFR inhibitor effective against T790M mutations (second line to Gefitinib)

Question 41

Pembrolizumab

Answer 41

Inhibits PD1 to block PD1+PDL1 interactions with T-cells

Question 42

atezolizumab

Answer 42

Inhibits PDL1 to block PD1+PDL1 interactions with T-cells

Question 43

Ipilimumab

Answer 43

Inhibits CTLA-4 on T-cells to enhance t-cell activation

Question 44

trastuzumab/pertuzimab

Answer 44

inhibits HER-2 to prohibit dimerization

Question 45

cetuximab

Answer 45

inhibits EGFR on B-cells -- blocks activation of EGFR kinase

Question 46

Bevacizumab

Answer 46

inhibits VEGF on B-cells (binds ligand)

Question 47

Ramucirumab

Answer 47

inhibits VEGF on B-cells (binds receptor)

Question 48

rituximab

Answer 48

inhibits CD20 on B-Cells

Question 49

daratumumab

Answer 49

inhibits CD38 on B-Cells

Question 50

trastuzumab/emtansine

Answer 50

transtuzimab: binds & inhibits HER2; emtansine: inhibits microtubule assembly

Question 51

trastuzumab/daruxecan

Answer 51

transtuzimab: binds & inhibits HER2; deruxecan: type 1 topoisomerase inhibitor

Question 52

Blinatumomab

Answer 52

brings T cells (by binding to CD3) to CD19 on B cell tumors

Question 53

mosunetuzumab

Answer 53

brings T cells (by binding to CD3) to CD20 on B cell tumors

Question 54

Teclistamab

Answer 54

brings T cells (CD3) to BCMA on myelomas

Question 55

taquetamab

Answer 55

brings T cell to GPCR C5D on myelomas

Question 56

Sipulecel-T

Answer 56

antigens on prostate cancer

Question 57

CAR-T

Answer 57

will bind cells with CD19 and kill them

Question 58

Olaparib

Answer 58

PARP inhibitor - Primarily used in cancers with BRACA 1/2 mutations (traps PARP to DNA)

Question 59

Palbociclib

Answer 59

CDK 4/6 kinase inhibitor (used in cancers with BRCA 1/2 mutations)

Question 60

5-Azacytosine

Answer 60

DNMT (DNA methyltransferase) inhibitor: incorporates into DNA or RNA and covalently binds DNMT enzymes to inhibit their function

Question 61

Venetoclax

Answer 61

BCL-2 inhibitor: drives cell death via apoptosis (BCL-2 is and anti-apoptotic protein often overexpressed in cancers)

Question 62

Pomalidomide

Answer 62

binds cereblon to induce ubitquitination and degradation of IKZF TFs, (important for lymphocyte development and cell survival in multiple myeloma)