Sept13 M2-Hormonal Cancer Therapies Flashcards
(40 cards)
HCT used in what 4 cancers
- testis
- ovary
- breast
- prostate
4 principles of use of HCT
- effective singly
- additive, synergistic
- non cumulative toxicity
- use at max tolerated dose
testis cancer origin and initial signal
- most probably dev in fetus
- initial signal is on germ cells
(imp) current tx for testis cancer
unilateral orchiectomy followed by chemo (BEP = 3 drugs given)
(important) 3 chemo drugs for testis cancer (note: all three are used at the same time**)
- bleomycin
- etoposide
- cisplatin
(imp) bleomycin MOA
- Abx. glycoprotein
- found to be antineoplastic
- causes ssDNA and dsDNA breaks
- inhibits DNA synthesis
topoisomerase function
enzyme that helps DNA not get overwound or underwound during replication
(imp) etoposide fct
topoisomerase II inhibitor
- complexes with it
- enhances dsDNA and ssDNA cleavage
- inhibits religation
(imp) cisplatin MOA
- heavy metal complex
- inoculating agent
- alkylating agent that racts with DNA to form intra and interstrand crosslinks
SEs of BEP in postsurgical chemo for testis cancer
- SE on dividing tissues (GI, repro, immune)
- sperm anomalies including aneuploidy
- infertility
2 most common types of ovarian cancers
- epithelial
- germ cell tumor
first line drug combination for epithelial cell cancer in ovaries
- CEP (is the same as BEP): cisplatin, etoposide, bleomycin + placlitaxel
- alternatives if this doesn’t work
SEs of CEP (BEP) for ovarian cancer
like BEP for testis cancer. nausea, vomiting, hair and apetite loss, rashes, mouth sores, dividing organs
(imp?) taxane (paclitaxel, taxol) MOA (chemo for ovarian epith ca)
stabilizes microtubules
-can’t breakdown during cell division, stabilizes the spindle
ovarian germ cell tumor first line drug combination + SEs
BEP (CEP)
- bleomycin
- etiposide
- cisplatin
- SEs still the same
main thing to do before chemo tx of testicular cancer for fertility
bank sperm before the start of the chemo
two most common cancers in life
prostate and breast
do androgens cause prostate cancer
no
are androgens needed for prostate ca
yes. Rs for testo and estradiol in prostate
- for testo = in stroma
- for E = in epithelium
mainstay of tx for prostate cancer
combination of:
- GnRH agonist that causes an increase in LH and spike in testo but eventually if give enough, testo prod goes down
- androgen R antagonist
how androgen R antag works
binds a peripheral allosteric site on the receptors, changes its structure, prevents testo binding
problem - reversible
other approaches to prostate tx
- block enzymes making testo into active steroids (finasteride inhibits 5 alpha reductase and DHT prod)
- block estrogen Rs (tamoxifen)
- block estrogen prod (aromatase inhibitors)
how tamoxifen works
- blocks partially but not completely the ER activity
- is a competitive partial agonist, antagonist at the estrogen R
- activity depends on ERalpha to ERbeta ratio in the cells
- supresses insulin-like GF (IGF-1)
- upregulates transforming GF beta (TGF-b)
management of ER+ breast cancer (chemo)
- aromatase inhibitor (after menopause)
- tamoxifen (anti-estrogen R)
