Exam 1 - Oncology (Endocrine) Flashcards
enzymes review:
cholesterol to pregnenolone
cholesterol side chain cleavage enzyme
enzymes review:
pregnenolone to 17a-hydroxypregnenolone
17a-hydroxylase
enzymes review:
17a-hydroxypregnenolone to dehydroepiandosterone
17,20-lyase
enzymes review:
testosterone to estradiol
aromatase
enzymes review:
testosterone to DHT
5a-reductase
enzymes review:
androstenedione to estrone
aromatase (CYP19)
Aromatase = CYP__
19
2 major strategies to endocrine therapy
- stop steroid receptor fxn
- decrease production of steroids
2 major classes used for endocrine therapy
aromatase inhibitors
SERMs?
poorly differentiated tumors are generally ______, _____ and ______
ER-, more sensitive to cytotoxic agents, spread/grow faster than well differentiated ones
Which hormone is produced in pituitary gland?
LH
more ER = _____ (better or worse) outcomes with endocrine therapy
better
triple negative tumors (ER-, PR-, HER2-) respond best to what type of therapies?
chemo
Luminal A (ER+/PR+) respond best to what type of therapies?
endocrine therapy (antiestrogen or aromatase inhibitor)
HER2+ responds best to what type of therapy?
trastuzumab
tamoxifen(Nolvadex) is:
-_____
-_____
-_____
-oldest, most used in ER+ breast cancer
-prodrug
-effective in post and premenopausal women
T/F: Tamoxifen can be used in high risk pts who don’t actually have cancer yet
T
CYP enzyme responsible for interaction w/ Tamoxifen
CYP2D6
agonist or antagonist?
-AIs
-SERMs
-SERDs
-agonist
-both
-antagonist
SERMs AE
hot flashes (antagonist effect)
increased coag/clots/VTE risk (agonist effect)
uterine endometrial hyperplasia (agoinst)
SERMs beneficial effects
prevents breast cancer (antagonist)
blocks bone resorption (agonist)
Fulvestrant
IM dosing
full SERD antagonist
postmenopausal women only
Elacestrant
-PO dosing
-partial agonist at low doses and full antagonist at high doses in terms of SERD activity
-postmenopausal women only
aromatase inhibitors primary target
peripheral adipose tissue (not ovary)
T/F: AIs are used in pre and post menopausal women
F (just post)
non-steroidal AIs AE
increased bone density loss (more fractures than tamoxifen)
Exemestane (Aromasin)
-inhibitor that binds irreversibly at active site and inactivates enzyme
-post menopausal only (2nd line)
Exemestane (Aromasin) AE
hot flashes
peripheral edema and weight gain
increased cholesterol levels
is slow release or fast preferred for GnRH analogs
slow, as fast would cause an increase in all steroid hormones (agonist)
GnRH analog AE
initial transient worsening of Sx
long term: hot flashes, sexual dysfxn
GnRH for pre or post
pre
for postmenopausal women w/ER+ we use:
tamoxifen
non-s AI (anastrazole, letrozole)
s AI (exemestane)
fulvestrant
for premenopausal we use:
GnRH agonists (goserelin and leuprolide)
surgical oophorectomy
tamoxifen
GnRH analogs in men for prostate cancer cause
initial transient increase in testosterone
long term: gynecomastia, sexual dysfxn
flare or no flare
-degarelix
-leuprolide
-relugolix
-goselerin
-triptorelin
-no flare
-flare
-no flare
-flare
-flare
Abiraterone (Zytiga) MOA
inhibits fxn of 17 a-hydroxylase and 17,20 lyase
-this causes more DHEA and androstenedione
common SE of abiraterone
increased cholesterol
enzalutamide, apalutamide, darolutamide uses
for metastatic and non-metastatic prostate cancer
mechanisms of resistance in endocrine therapy
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
