Exam 1 - Oncology (kinase inhibitors)

Question 1

what is unique about the action of the tamoxifen as compared to Fluvestrant?
a. it leads to ER degradation
b. it holds ER out of the nucleus
c. it ejects ER from the cell
d. it activates ER in bone

Answer 1

d. it activates ER in bone

Question 2

which of the following is not a hormone responsive cancer type?
a. breast
b. ovarian
c. prostate
d. endometrial

Answer 2

b. ovarian

Question 3

which of the following is used only in the postmenopausal setting?
a. Letrozole
b. Tamoxifen
c. Leuprolide
d. Raloxifene

Answer 3

a. Letrozole

Question 4

which compound acts directly on AR?
a. Leuprolide
b. Abiraterone
c. Degarelix
d. Enzalutamide

Answer 4

d. Enzalutamide

Question 5

molecular causes of cancer

Answer 5

cancer is a breakdown of cellular maintenance that may be manifested by several causes
signal transduction through kinases drives proliferation

Question 6

do better therapeutic agents target one kinase pathway or multiple?

Answer 6

multiple

Question 7

kinases are _____

Answer 7

highly abundant proteins

Question 8

9 tyrosine kinase inhibitors

Answer 8

imatinib
ibrutinib
dasatinib
ceritinib
lenvatinib
tofacitinib
ruxolitinib
lapatinib
pazopanib

Question 9

4 serine/threonine kinase inhibitors

Answer 9

palbociclib
trametinib
vemurafenib
dabrafenib

Question 10

2 dual protein kinase inhibitors

Answer 10

regorafenib
sorafenib

Question 11

do kinase inhibitors have diverse or similar structures

Answer 11

diverse

Question 12

genomic DNA from lung cancer biopsies are tested via ____ for a particular mutation of EGFR
if positive, these pts will go on ______ therapies

Answer 12

PCR, anti-EGFR

Question 13

substrate for every kinase

Answer 13

ATP

Question 14

what makes tyrosine a good (and common) target of several kinases?

Answer 14

can be phosphorylated at -OH group

Question 15

other targets of kinases

Answer 15

serine, threonine, and lipids

Question 16

cell signaling is ____ (complex or simple)

Answer 16

complex

Question 17

describe the general structure of kinases

Answer 17

N and C groups connected by a hinge region
activation loop controls access to the active site

Question 18

3 types of kinase inhibitors and differences btwn them

Answer 18

type 1: bind to active conformation of kinase
type 2: bind and stabilize the inactive conformation of kinase
type 3: occupy an allosteric pocket outside of the ATP-binding pocket

Question 19

competitive vs. covalent inihbitors

Answer 19

competitive inhibitors compete with ATP in a reversible fashion
covalent is irreversible (stronger bond)

Question 20

which amino acid is not a target of phosphorylation?
a. tyrosine
b. serine
c. threonine
d. alanine

Answer 20

d. alanine (only has methyl side group, not as reactive)

Question 21

what is the source of the phosphate that gets transferred onto a substrate by a kinase?
a. SAM
b. DNA
c. RNA
d. ATP

Answer 21

d. ATP

Question 22

most commonly mutated growth factor in lung cancer

Answer 22

EGFR

Question 23

T/F: Gefitinib. requires genetic test before prescribing

Answer 23

T

Question 24

Gefitinib and Erlotinib indication

Answer 24

EGFR mutant metastatic NSCLC

Question 25

Gefitinib (IRESSA) and Erlotinib fxn thru ____ kinase activity

Answer 25

tyrosine

Question 26

EGFR signaling induces cell ____. inhibition of kinase activity turns ___ signal to _____

Answer 26

proliferation, off, proliferate

Question 27

AE of Gefitinib and Erlotinib

Answer 27

fatigue, rash, diarrhea

Question 28

Afatinib (Gilotrif) indication

Answer 28

EGFR mutant NSCLC

Question 29

Afatinib (Gilotrif) is what type of inhibitor

Answer 29

covalent inhibitor of all ErbB receptors

Question 30

Explain how EGFR inhibitor associated skin rash can be a good thing

Answer 30

If rash seen (normally on chest/neck area), pts tend to respond better to therapy and live longer

Question 31

T790M mutation is associated with drug _______ (resistance or sensitivity)

Answer 31

resistance (this one specifically causes resistance to Gefitinib)

Question 32

L858R is commonly associated with drug _______ (resistance or sensitivity)

Answer 32

sensitivity

Question 33

drug to give pt if T790M mutation found

Answer 33

Osimertinib (third gen. EGFR inhibitor)

Question 34

type of bond Osimertinib forms

Answer 34

covalent

Question 35

Lapatinib (Tykerb) MOA

Answer 35

small molecule tyrosine kinase inhibitor that blocks HER2 and EGFR signaling

Question 36

Lapatinib (Tykerb) indication

Answer 36

approved (in combo with capecitabine) for tx of advanced metastatic breast cancer in pts whose cancer has progressed on other therapies

Question 37

Lapatinib (Tykerb) bond (and what it binds to)

Answer 37

reversible inhibitor of EGFR and HER2Lapatinib (Tykerb) indication

Question 38

Lapatinib (Tykerb) is selective for HER2 or EGFR?

Answer 38

HER2

Question 39

SE of Lapatinib (Tykerb)

Answer 39

NVD - watch for sx of CHF too

Question 40

Tucatinib (Tukysa) use

Answer 40

for tx of HER2+ breast cancer -2nd line therapy

Question 41

FLT3 inihibitors -1st gen: ______ is _____ kinase inhibitor

Answer 41

midostaurin is broad

Question 42

FLT3 inihibitors -2nd gen: ______ is _____ kinase inhibitor

Answer 42

crenolanib is more specific

Question 43

FLT3 inihibitors -type 2: ______ is _____ kinase inhibitor

Answer 43

Quizartinib is specific for ITD mutations

Question 44

Imatinib (Gleevec) MOA and reasoning

Answer 44

type 2 small molecule inhibitor of the Abl tyrosine kinase. activity of Bcr-Abl chimeric protein is constitutively active which results in malignancy -primarily treats CML

Question 45

Imatinib (Gleevec) AE

Answer 45

N/V fluid retention and edema neutropenia and thrombocytopenia frequent but mild resistance is constant battle

Question 46

Ponatinib (Iclusig) use

Answer 46

BCR-Abl inhibitor effective against all major mutant forms of BCR-Abl

Question 47

drug approved for ALK mutation in NSCLC who have progressed or are intolerant to crizotinib

Answer 47

Alectinib (Alecensa)

Question 48

Trametinib (Mekinist) MOA

Answer 48

inhibits kinase activity of MEK1 and MEK2 -type 3 inhibitor

Question 49

cannot use what drug if pt has history of BRAF inhibitor therapy

Answer 49

trametinib

Question 50

Trametinib (Mekinist) AE

Answer 50

rash diarrhea lymphedema

Question 51

Acalabrutinib

Answer 51

2nd gen covalent BTK inhibitor -more potent and more selective than 1st gen ibrutinib -indication is B cell lymphoma (MCL and CLL)

Question 52

rapamycin analogues

Answer 52

-aka: Sirolimus -mTOR is a serine-threonine kinase -inhibits immune response by blocking IL-2 signaling tranduction

Question 53

T/F: Everolimus inhibits mTORC1 and mTORC2

Answer 53

F, only mTORC1

Question 54

biggest problem with kinase inhibitors

Answer 54

resistance -they are not curative therapy