Exam 1 - Oncology (Endocrine)

Question 1

enzymes review:
cholesterol to pregnenolone

Answer 1

cholesterol side chain cleavage enzyme

Question 2

enzymes review:
pregnenolone to 17a-hydroxypregnenolone

Answer 2

17a-hydroxylase

Question 3

enzymes review:
17a-hydroxypregnenolone to dehydroepiandosterone

Answer 3

17,20-lyase

Question 4

enzymes review:
testosterone to estradiol

Answer 4

aromatase

Question 5

enzymes review:
testosterone to DHT

Answer 5

5a-reductase

Question 6

enzymes review:
androstenedione to estrone

Answer 6

aromatase (CYP19)

Question 7

Aromatase = CYP__

Answer 7

19

Question 8

2 major strategies to endocrine therapy

Answer 8

1. stop steroid receptor fxn
2. decrease production of steroids

Question 9

2 major classes used for endocrine therapy

Answer 9

aromatase inhibitors
SERMs?

Question 10

poorly differentiated tumors are generally ______, _____ and ______

Answer 10

ER-, more sensitive to cytotoxic agents, spread/grow faster than well differentiated ones

Question 11

Which hormone is produced in pituitary gland?

Answer 11

LH

Question 12

more ER = _____ (better or worse) outcomes with endocrine therapy

Answer 12

better

Question 13

triple negative tumors (ER-, PR-, HER2-) respond best to what type of therapies?

Answer 13

chemo

Question 14

Luminal A (ER+/PR+) respond best to what type of therapies?

Answer 14

endocrine therapy (antiestrogen or aromatase inhibitor)

Question 15

HER2+ responds best to what type of therapy?

Answer 15

trastuzumab

Question 16

tamoxifen(Nolvadex) is:
-_____
-_____
-_____

Answer 16

-oldest, most used in ER+ breast cancer
-prodrug
-effective in post and premenopausal women

Question 17

T/F: Tamoxifen can be used in high risk pts who don’t actually have cancer yet

Answer 17

T

Question 18

CYP enzyme responsible for interaction w/ Tamoxifen

Answer 18

CYP2D6

Question 19

agonist or antagonist?
-AIs
-SERMs
-SERDs

Answer 19

-agonist
-both
-antagonist

Question 20

SERMs AE

Answer 20

hot flashes (antagonist effect)
increased coag/clots/VTE risk (agonist effect)
uterine endometrial hyperplasia (agoinst)

Question 21

SERMs beneficial effects

Answer 21

prevents breast cancer (antagonist)
blocks bone resorption (agonist)

Question 22

Fulvestrant

Answer 22

IM dosing
full SERD antagonist
postmenopausal women only

Question 23

Elacestrant

Answer 23

-PO dosing
-partial agonist at low doses and full antagonist at high doses in terms of SERD activity
-postmenopausal women only

Question 24

aromatase inhibitors primary target

Answer 24

peripheral adipose tissue (not ovary)

Question 25

T/F: AIs are used in pre and post menopausal women

Answer 25

F (just post)

Question 26

non-steroidal AIs AE

Answer 26

increased bone density loss (more fractures than tamoxifen)

Question 27

Exemestane (Aromasin)

Answer 27

-inhibitor that binds irreversibly at active site and inactivates enzyme -post menopausal only (2nd line)

Question 28

Exemestane (Aromasin) AE

Answer 28

hot flashes peripheral edema and weight gain increased cholesterol levels

Question 29

is slow release or fast preferred for GnRH analogs

Answer 29

slow, as fast would cause an increase in all steroid hormones (agonist)

Question 30

GnRH analog AE

Answer 30

initial transient worsening of Sx long term: hot flashes, sexual dysfxn

Question 31

GnRH for pre or post

Answer 31

pre

Question 32

for postmenopausal women w/ER+ we use:

Answer 32

tamoxifen non-s AI (anastrazole, letrozole) s AI (exemestane) fulvestrant

Question 33

for premenopausal we use:

Answer 33

GnRH agonists (goserelin and leuprolide) surgical oophorectomy tamoxifen

Question 33

GnRH analogs in men for prostate cancer cause

Answer 33

initial transient increase in testosterone long term: gynecomastia, sexual dysfxn

Question 34

flare or no flare -degarelix -leuprolide -relugolix -goselerin -triptorelin

Answer 34

-no flare -flare -no flare -flare -flare

Question 35

Abiraterone (Zytiga) MOA

Answer 35

inhibits fxn of 17 a-hydroxylase and 17,20 lyase -this causes more DHEA and androstenedione

Question 36

common SE of abiraterone

Answer 36

increased cholesterol

Question 37

enzalutamide, apalutamide, darolutamide uses

Answer 37

for metastatic and non-metastatic prostate cancer

Question 38

mechanisms of resistance in endocrine therapy

Answer 38

mutations in AR that prevent binding of AR antagonists -this is preferred over CRPC (castration resistant prostate cancer) because it is more dangerous, resistant and aggressive