Signal Transduction I Flashcards
Huggins
1966, hormone deprivation as a treatment for hormone driven cancer.
3 ways to lower hormone concentration
decrease synthesis
Increase catabolism
neutralizing Ab to soak up hormone
2 ways to decrease hormone synthesis
turn down synthesis stimulation
drug directed-based interaction
LHRH Superagonist Mech
binds very strongly to LHRH receptor
LHRH Analog names
leuprolide
goserlin
What happens when LHRH superagonist binds?
Immediate increase in LH and testosterone
Then a fall to castrate levels
(things don’t like to be ovedriven)
LHRH side effects
medications, none
hypogonal, miserable
LHRH long term
iatrogenic osteoporosis
insulin resistence
Dagarelix (firmagone)
LHRH antagonist
Starting point for all sex hormones
cholesterol
17-lyase inhibition consequence
decrease in androgen like hormones
diminished cortisol
Lyase inhibitor
Abiraterone
What is given with abiraterone
adrenocorticoids (need physiological replacement)
Block testosterone by…
Conversion to T to DHT
Block androgen receptor
Anti-androgen (2)
Bicalutamide
Enzalutamide
Estrogen lowering drugs
Leuprolide Lysase inhibitors (not FDA approved)
Best target for estrogen synthesis inhibition?
Aromatase (minimal tweaking of other hormones)
Aromatase inhibitors
Anastrozole
Exemestane
Anastrozole side effects
arthralgia and myalgia
Exemestane
Suicide substrate
arthralgia and myalgia
Tamoxifen
Selective Estrogen receptor modulator (SERM)
How is Tamoxifen selective
Partial antagonist to certain isoforms
blocks breast form well
agonist in bone and uterus
Tamoxifen problem
Endometrial cancer (agonist in uterus)
Fulvestrant
pure ER antagonist
outperforms Tamoxifen
