Flashcards in 20. hormone therpay for cancer Deck (75)
what was John hunter the first person to suggest in 1786?
that the testes produced something that regulated the size of the prostate - when this was removed testes were small
>linked the size of the prostate with the function of the gonads
what does castration lead to in terms of hormones? how was this done and how is this done now?
removal of 95% of androgens - this process is still done now if a quick solution is needed but now we do it chemically
what are breast and prostate cancer initially? and what does this mean can be used?
hormone dependent for growth
>hormone antagonists can be used to effectively treat these cancers e.g. tamoxifen
after hormone therapy, what may occur?
may recur in an aggressive form that is now hormone resistant and does not response to antagonist therapy
where do >90% of breast and prostate cancer arise? and what do these express?
the epithelial cells population
what receptors do breast epithelial cells express?
ER and AR
what do almost all primary metastatic prostate tumours retain? and how is this seen in 50% of cases?
>amplified - exploiting androgen signalling for growth
what do not all breast cancer express?
ER - they are more heterogeneous than prostate
what is seen in over 50% of breast cancers?
what is used as a prognostic and predictive indicator in breast cancer?
>generally ER+ tumours are well-differentiated and prognosis is better, they are more treatable
how is ER status determined?
what % of ER+ and ER- breast cancers show positive response to oestrogen withdrawal?
5-10% - might not detect ER in this case/there is a second ER that is not screened for
what are ER- tumours unlikely to respond to? what therapies can be used in these cases?
oestrogen withdrawal or anti-oestrogen therapies
>chemotherapy and radiotherapy
what hormone therapies can be done for breast and prostate cancer? (4)
1. ovarian/testicular ablation
2. enzyme inhibition to prevent secondary/peripheral steroid conversion
3. steroid receptors antagonists (antioestrogen/antiandrogens)
4.inhibition of adrenal androgen synthesis
how is ovarian/testicular ablation do?
either through surgery or GnRH agonist (pituitary down regulation) - blocks production of oestrogen/androgens
what does the hypothalamus release? and how it is released?
>released in pulses
what does the pituitary gland release?
what happens between pulses of LHRH normally?
receptors on the pituitary gland are degraded and remade
how does pituitary down-regulation (chemical castration) work?
>patient given LHRH analogue
>this acts on pituitary gland
>initial rise in LH, testosterone and oestrogen
>LHRH signal remains constant and so receptors are degraded
>after 2 weeks no LH or testosterone (similar levels to castration)
why do some people still require castration?
due to this two week time lag
what % of androgens are released from testes, how much DHT is left in tissue and what implication does this have?
often combined with other therapies
how do 5α-reductase inhibitor work?
inhibits the conversion of testosterone to 5α-dihydroxytestosterone.
this binds androgen receptors with 10 times higher affinity
>inhibiting enzyme can block tumour growth
what is Guevedoces?
2% of births in a tribe in the Dominican republic are born female with internalised genitalia but develop into man due to surge in testosterone at puberty
>due to alpha reductase deficiency
>have small semi-functional prostate
how do aromatase inhibitors work?
>catalyses the conversion of testosterone to oestradoil
>reaction occurs in fat cells and accounts for 30% of oestrogen in circulation
what percentage of breast carcinoma cells contain increased levels of aromatase?
60-70% – they make their own oestrogen to feed their growth
what do hormone antagonists do?
antioestrogens/antiandrogens bind to receptors and inhibit steroid receptors meditated action (cell division and growth)
what affect can hormone antagonists also have?
some have agonist effect i.e. can activate the receptor, under some circumstances
name an ER antagonist
what affect does tamoxifen have?
inhibits the growth of the oestrogen receptor positive breast cancer cells