lecture 2 mabe Flashcards
what is the function of 5a-reductase?
turns test into DHT
what is the function of aromatase?
turns androtenedione into estrone and testosterone into estradiol
what CYP is aromatase?
CYP19
what are the two stratgies in endocrine therapy?
stop steroid receptor function
decrease production of steroids
estrogen receptors primarily bind estrogen where in the cell?
cytoplasm
how will ER+ tumors be treated?
endocrine therapy
what are the 4 distinct diseases in breast cancer?
claudin low: treated with cytotoxic
BRCA1: tumor supressor
HER2-enriched: RTK
luminal A+B
what drug is a SERM?
tamoxifen
what is tamoxifen used for?
resected and metastatic ER+/PR+ breast cancer
what cyp coverts tamoxifen and to what?
CYP2D6 converts it to high affinity hydroxylated and demethylated metabolites
translocation and DNA binding in a tissue-specific manner
what are the antagonist and agonist effects of tamoxifen?
antagonist: blocks estrogen-dependent breast cancer cell proliferation. hot flashes
agonist: 3x endometrial cancer, preserve BMD
what was the first drug approved for breast cancer prevention in high-risk patients?
tamoxifen
what are SERDs?
fluvestrant and elacestrant
what is fluvestrant’s MOA? IM
pure ER antagonist (no agonist effects)
what is elacestrant MOA? PO
full SERD at high doses
partial agonist at low doses
what are SERDs (fluvestrant + elacestrant) approved for?
approved for ER+ metastatic breast cancer in postmenopausal women who progressed on other antiestrogen therapy
what are the source of estrogen in postmenopausal women?
adipocytes
aromatase in adipocytes convert androtendione to estrone
what is primary target for aromatase?
peripheral (adipose) tissue, not ovary
what is primary application of aromatase?
estradiol suppression in postmenopausal women
what are non-steroidal aromatase inhibitors?
letrozole and anastrozole
letrozole and anastrozole uses?
potent + selective inhibitor or aromatase
primary indication: breast cancer in postmenopausal women
firstline or when started 3-5 years after tamoxifen
what are steroidal aromatase inhibitors?
exemestane
exemestane pharmacology?
suicide inhibitor
binds irreversibly @ active site and inactivates
indication: tx estrogen-responsive breast cancer postmenopausal women
FSH + LH importance?
chronic admin of GnRH analogs –> downregulate GnRH receptor
decreased FSH –> decrease aromatase and estrogen
