Anti- cancer endocrine therapies

what else is the enzyme aromatase called

CYP19

corticosteroid with anti cancer effect in blood cancers

dexamethasone

how else can glucocorticoids be used in cancer care

as palliative care and to reduce hypersensitivity reactions

what type of cancers can use hormonal therapies as treatment

hormone dependent cancers (breast, prostate, endometrial)

what are the two hormones mainly targeted by hormonal therapies

estradiol and dihydrotestosterone

what are the two major strategies of endocrine therapy

stop steroid function

decrease production of steroids

Where is GnRH produced?

hypothalamus

where is LH/FSH produced

pituitary gland

what kind differentiation is more likely in ER+ cancer

well differentiated tumors (better prognosis)

which type of tumors are more sensitive to cytotoxic agents and why

poorly differentiated (ER-)

which types of tumors are more likely to respond to hormone therapy

ER+

which types of tumors respond best the chemotherapy

triple negative (very high grade and poorly differentiated)

best treatment for luminal A tumors

endocrine therapy

prodrug endocrine therapy and what it must be metabolized to

tamoxifen --> endoxifen

which enzymes activate tamoxifen

CYP3A4 and CYP2D6

tamoxifen drug class

SERM

what determines the effects of tamoxifen

tissue dependent

estrogen antagonist effects of tamoxifen

block estrogen dependent breast cancer cell proliferation

hot flashes

estrogen agonist effects of tamoxifen

increased endometrial cancer risk

preservation of bone density

what stage of menopause must women be in to use tamoxifen

pre or post menopausal

treatment indication of tamoxifen

resected or metastatic ER+/PR+ breast cancer

what makes tamoxifen less effective

patients with a CYP2D6 variant

difference between tamoxifen and raloxifene

No endometrial hyperplasia with raloxifene

MOA of SERDs

degrades estrogen receptors

what are the SERDs

Fulvestrant and elacestrant

administration for fulvestrant vs elacetrant

fulvestrant= IM

elacetrant= PO

who are SERDs used to treat

treatment of ER+ metastatic breast cancer in postmenopausal women

pure ER antagonist (PROTAC) drug

vepdegestrant

MOA of vepdegestrant

binds to ER and E3 ligase, E3 ligase ubiquinates ER which forces degradation

how does aromatase convert androgens into estrone

oxidizes steroid hormone, then demethylates

who can use aromatase inhibitors and why

postmenopausal women- primary target of inhibitors is in adipose tissue, not ovaries and adipocytes are a source of estrogen in postmenopausal women

non-steroidal aromatase inhibitors

Anastrozole

Letrozole

non-steroidal are what type of aromatase inhibitor

competitive inhibitors of aromatase activity

when can non-steroidal aromatase inhibitors be used

first line therapy OR after 3-5 years of tamoxifen therapy in post menopausal women

steroidal aromatase inhibitors

Exemestane

Androstenedione

MOA of exemestane

acts as false substrate that aromatase converts to reactive intermediate, intermediate binds irreversibly at active site and inactivates enzyme

indication of exemestane

treatment of estrogen responsive breast cancer in postmenopausal women

toxicities of exemestane

hot flashes, peripheral edema, weight gain, increased cholesterol levels

how to downregulate pituitary GnRH receptors

chronic administration of GnRH leading to pituitary desensitization

what type of drugs are GnRH analogs and how must they be administered

peptides with modified amino acids, SQ injection

what happens acutely with administration of GnRH

surge of LH and FSH, increase in tumor growth

how are GnRH analogs effective in treating cancer

downregulates GnRH receptors --> severe loss of estrogen --> inhibition of estrogen dependent breast cancers

what are the GnRH analogs

leuprolide acetate, goserelin, triptorelin

long term side effects of GnRH analogs

hot flashes, sexual dysfunction

primary indication of GnRH analogs

premenopausal breast cancer

which hormonal therapies should be used in post menopausal women with ER+ cancer

tamoxifen, non steroidal + steroidal aromatase inhibitors, pure anti-estrogens

which hormonal therapies should be used in premenopausal women

GnRH agonists, surgical oophorectomy, tamoxifen

how is prostate cancer staged

Gleason score (1= well differentiated, 5= poorly differentiated)

most important risk factor of prostate cancer

age (after age 40 especially)

blood serum levels of what can indicate prostate cancer

prostate specific antigen (PSA)

what level of PSA may be suggestive of prostate cancer

>6.5 ng/mL

what drug class can be used to result in "chemical castration" in men with prostate cancer

GnRH analogs

primary indication of GnRH analogs in men

palliative treatment of advanced prostate cancer

long term side effects of GnRH analogs in men

gynecomastia, sexual dysfunction

GnRH antagonists

Degarelix

Relugolix

primary indication of GnRH antagonists

advanced prostate cancer

other name for 17a-hydroxylase and 17,20 lyase

CYP17

role of CYP17

converts progesterones to androgens

enzyme inhibitor drug that inhibits the function of 17a hydroxylase and C17,20 lyase

abiraterone

what type of drug is abiraterone

steroid analogue

androgen receptor antagonists

Enzalutamide

Apalutamide

Darolutamide

MOA of androgen receptor antagonists

prevent AR translocation to the nucleus, inhibits AR binding to DNA

how can prostate cancer become resistant to therapy

mutations in AR can arise leading to androgen independent activation

what is prostate cancer called when it is androgen independent

castration resistant prostate cancer (CRPC)