Hormone therapy of prostate cancer

Question 1

what receptors stimulate prostate cancer

Answer 1

Androgens

Question 2

what is first line for treatment for advanced prostate cancer?

Answer 2

Androgen deprivation therapy

Question 3

Androgen deprivation therapy is not curative but prolongs survival?

Answer 3

Via surgical castration or medical castration using GnRH agonist or antagonist

Question 4

Second line treatment for prostate cancer

Answer 4

antiandrogens=competitive antagonists of androgens at the AR
Estrogens
Inhibitors of steroidogenesis

Question 5

Androgen independent is when

Answer 5

patients become refractory to further hormonal therapies

Question 6

AE of androgen deprivation?

Answer 6

vasomotor instability
increased risk for diabetes and coronary heart disease
give bisphosphonate therapy

Question 7

Antiandrogens vs GnRH agonists

Answer 7

cause more gynecomastia, mastodynia, and hepatotoxicity BUT LESS vasomotor flashing and loss of bone mineral density

Question 8

In patients with prostate cancer, estrogen?

Answer 8

cause a hypercoagulable state and increase cardiovascular mortality and are not standard treatment options

Question 9

Gonadotropin releasing hormone receptor is expressed on?

Answer 9

pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate

Question 10

Prolonged exposure of GnRH agonists leads to?

Answer 10

a downregulation effect resulting in hypogonadism (suppression of testosterone)

Question 11

GnRH antagonists MOA?

Answer 11

blocks the receptor and inhibits Gonadotropin release

Question 12

Drugs that are GnRH antagonist?

Answer 12

Degarelix

Question 13

Drugs that are GnRH agonist?

Answer 13

leuprolide, gosrelin, triptorelin, histrelin, and nafarelin

Question 14

GnRH agonists Toxicity

Answer 14

transient rise in LH, the testosterone surge may induce acute stimulation of prostate cancer growth and a flare of symptoms from metastatic deposits

Question 15

Flare Phenomenon can be fixed with?

Answer 15

oral antiandrogen therapy which will inhibit the action of the increased serum testosterone levels

Question 16

Degarelix is not associated with

Answer 16

systemic allergic reactions

Question 17

Antiandrogens MOA?

Answer 17

bind to AR->competively inhibits binding of testosterone and dihydrotestosterone (DHT)–>preventing AR nuclear translocation–>inhibiting transcription of downstream androgen responsive genes

Question 18

Antiandrogen therapy alone?

Answer 18

does not decrease LH prodcution

Question 19

Antiandrogen therapy is typically given with

Answer 19

ADT

Question 20

Antiandrogens steroidal?

Answer 20

cyproterone

Question 21

Antiandrogens nonsteroidal?

Answer 21

enzalutamide, flutamide, bicalutamide, and nilutamide

Question 22

Drug that is second generation synthetic nonsteroidal antiandrogen?

Answer 22

Enzalutamide

Question 23

Enzalumatide does what?

Answer 23

induces cell apoptosis
prevents binding of androgens to the AR

Question 24

Enzalumatide undergoes CYP2C8 leading to ______

Answer 24

active metabolite (N-desmethyl enzalutamide)

Question 25

Enzalutamide AE

Answer 25

Hot flashes
crosses BBB leading to seizures

Question 26

AR signaling supports continued prostate cancer cells

Answer 26

in:
androgens produced from nongonadal sources(the adrenal glands and prostate cancer cells)
androstenedione produced by adrenal glands is converted to testosterone in peripheral tissues and tumors
AR gene mutations
intratumoral de novo androgen synthesis

Question 27

ketoconazole

Answer 27

inhibitor for CYP 11A and CYP 17 producing dehydroepiandrosterone (DHEA) and androstenedione

Question 28

Abiraterone

Answer 28

irreversible inhibitor of 17a-hydroxylase and CYP 17A1 activity in testicular, adrenal, and prostatic cancer tissue—>reduces the synthesis of DHEA and androstenedione

Question 29

Abiraterone Acetate turns into

Answer 29

Abiraterone (active metabolite)

Question 30

Abiraterone toxicity?

Answer 30

hepatotoxicity

Question 31

Abiraterone Resistance

Answer 31

tumor cells expressing constitutively active AR splice variants

Question 32

CYP17 Inhibitors aka drugs that inhibit androgen synthesis?

Answer 32

Ketoconazole and Abiraterone

Question 33

High estrogen levels can

Answer 33

reduce testosterone to castrate levels via negative feedback on the HPA
May also compete with androgens for steroid HRs and exert cytotoxic effect on PA cancer cells