Endocrine Cancer Mabe

Question 1

Which hormone is produced in the pituitary gland?

a. GnRH
b. LH
c. estrogen
d. progesterone

Answer 1

b. LH

Question 2

Estrogen receptor primarily binds estrogen where in the cell?

a. On the plasma membrane
b. In the mitochondria
c. In the cytoplasm
d. In the nucleus

Answer 2

c. In the cytoplasm
(once bound moves into nucleus)

Question 3

What enzyme converts androstenedione to estrone?

a. CYP19
b. 5alpha-reductase
c. 17, 20 lyase
d. P450scc

Answer 3

a. CYP19 (aromatase)

Question 4

Which compound directly inhibits the activity of the estrogen receptor throughout the body?

a. Letrozole
b. Exemestane
c. Tamoxifen
d. Fulvestrant

Answer 4

d. Fulvestrant

(a and b are indirect; c can do some but not all tissues)

Question 5

Which compound is referred to as a SERM?

a. Letrozole
b. Exemestane
c. Tamoxifen
d. Fulvestrant

Answer 5

c. Tamoxifen

Question 6

What is unique about the action of the Tamoxifen as compared to Fulvestrant?

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 6

d. It activates ER in bone marrow

(fulvestrant degreades)

Question 7

Which of the following is not a hormone responsive cancer type?

a. Breast cancer
b. Ovarian cancer
c. Prostate Cancer
d. Endometrial cancer

Answer 7

b. Ovarian cancer

Question 8

Which of the following is only used in the postmenopausal setting?

a. Letrozole
b. Tamoxifen
c. Leuprolide
d. Raloxifene

Answer 8

a. Letrozole

Question 9

Which compound acts directly on AR?

a. Leuprolide
b. Abiraterone
c. Degarelix
d. Enzalutamide

Answer 9

d. Enzalutamide

Question 10

glucocorticoids have anti-cancer effect in tx of blood cancers including which 3? (slide 4)

Answer 10

-pediatric acute lymphoblastic leukemia (ALL)
-multiple myeloma
-lymphomas

Question 11

which is NOT one of the 3 most common glucocorticoids used for cancer?

a. dexamethasone
b. budesonide
c. prednisolone
d. methylprednisolone

Answer 11

b. budesonide

Question 12

3 hormone-dependent cancers (slide 5)

Answer 12

breast, prostate, and endometrial cancer

Question 13

hormonal therapies primarily target _______ (breast, endometrial) and __________ (prostate)

Answer 13

estradiol; dihydrotestosterone

Question 14

two strategies to endocrine therapy (slide 8)

Answer 14

1. stop steroid receptor function
2. dec production of steroids

Question 15

where is GnRH produced?

Answer 15

hypothalamus

Question 16

Well differentiated tumors are more likely to be ____; poorly differentiated tumors are generally ____

a. ER- ; ER+
b. ER+ ; ER-
c. ER- ; ER-
d. ER+ ; ER+

Answer 16

b. ER+ ; ER-

Question 17

T or F: hormone therapy in breast cancer is generally limited to ER+/PR+ tumors

Answer 17

T

Question 18

4 molecular subtypes of breast cancer (slide 16)

Answer 18

Triple negative/Basal-like
HER2-enriched
Luminal B
Luminal A

Question 19

T or F: tamoxifen is a prodrug

Answer 19

T

Question 20

tamoxifen must be metabolized to _______ by 2D6, then to ________ by 3A4

Answer 20

4OH-TAM; endoxifen

Question 21

2 estrogen antagonist effects of tamoxifen

Answer 21

-blocks estrogen-dependent breast cancer cell proliferation
-hot flashes due to anti-estrogen effects

Question 22

2 estrogen agonist effects of tamoxifen

Answer 22

-incidence of endometrial cancer inc 3-fold
-preservation of bone density in postmenopausal women

Question 23

T or F: tamoxifen is only effective in postmenopausal women

Answer 23

F (pre- and post-)

Question 24

first drug approved for breast cancer prevention in high-risk pts

a. raloxifene
b. fulvestrant
c. letrozole
d. tamoxifen

Answer 24

d. tamoxifen

(reduces risk by 50%)

Question 25

T or F: fulvestrant has only agonist effects

Answer 25

F (pure ER antagonist, NO agonist effects)

Question 26

Fulvestrant and Elacestrant drug class

Answer 26

SERD

Question 27

T or F: primary target of aromatase inhibitors are the ovaries

Answer 27

F (peripheral tissue/adipose tissue)

Question 28

aromatase inhibitors primary application is estradiol suppression in ___________ women a. premenopausal b. postmenopausal c. both

Answer 28

b. postmenopausal

Question 29

2 non-steroidal aromatase inhibitors

Answer 29

anastrazole, letrozole

Question 30

Letrozole and anastrozole are __________ inhibitors or aromatase activity a. non-competitive b. competitive

Answer 30

b. competitive

Question 31

what drug is a steroidal aromatase inhibitor?

Answer 31

exemestane

Question 32

exemestane is structurally related to what molecule?

Answer 32

androstenedione

Question 33

T or F: adipocytes are a source of estrogen in postmenopausal women

Answer 33

T

Question 34

does exemestane's intermediate bind reversibly or irreversibly at the active site?

Answer 34

irreversibly