B8.039 Prework 2: Mechanisms of Action of Tamoxifen, AIs, and Fulvestrant Flashcards
mechanism of action of tamoxifen
competitive binding to the estrogen receptor resulting in reduction of transcription of estrogen related genes
net result of tamoxifen use
block in the G1 phase of the cell cycle and a slowing of cell proliferation
CYTOSTATIC
-no killing
tamoxifen metabolism
CYP2D6
metabolites mediate the action due to their higher binding affinity
antagonist effects of tamoxifen
tumor inhibition in breast
hot flashes
agonist effects of tamoxifen
potential tumor stimulation
increased risk of endometrial cancer and thromboembolic effects
lowers cholesterol
preserves bone density
mechanism of AIs
inhibit aromastase enzyme selectively by blocking the heme moiety
suppress estrogen levels >90-95%
different types of AIs
steroidal (irreversible) -exemestane nonsteroidal (reversible) -anastrozole -letrozole
mechanism of fulvestrant
pure antagonist
- high affinity for ER
- blocks ER mediated transcription
- ER degradation and downregulation due to conformation change
indications for fulvestrant
second line if other antiestrogen therapy fails
mechanism of trastuzumab
monoclonal antibody that binds to the receptor to keep a ligand from binding, thus blocking dimerization of Her2 with Her3
**inhibition of ligand-independent signaling
use of trastuzumab
metastatic and early state Her2+ BC
combined with chemo increases overall survival and reduces relapse compared to chemo alone
pertuzumab mechanism
inhibits formation of ligand-dependent heterodimers of Her2 and Her1/3/4
**inhibition of ligand-dependent signaling
lapatinib mechanism
inhibition of tyrosine kinase activity of Her2 dimer
**inhibition of ligand-dependent and ligand-independent signaling
