Question:
Many times it has been said on this group that the body's feedback
mechanisms will always eventually overcome antiandrogens. So for
instance systemic anti androgens have limited use in prostate cancer
patients, correct?
However, I remember hearing in my state (texas) a while back a debate
about so called "chemical castration" as a possible forced treatment of
habitual sex offenders. How can this even be possible if the AA's are
always eventually overcome? Further, I heard it stated that eventually
chemical castration eventually becomes irreversible when used long
term. Neither of these jive with the contention that the body
eventually overcomes AA's. So what is the deal?
Also I have another totally off topic Q. If one was to have skin cancer
spread to the testicles, would it behave like testicular cancer, ie
increasing testosterone in the body, or not, presumably because it's
still skin cancer not testicular cancer? I read that skin cancer spread
to other organs needs to be treated differently than cancer that
originates in said organs. I'm just curious on that one.
Answer:
Most prostate cancers being treated with androgen ablation therapy will
eventually become androgen insensitive. Androgen responsive genes
somehow become activated despite the presence of antiandrogens. The
reasons for this are currently being researched. It is possible that the
androgen receptor (AR) becomes mutated so that the antiandrogens no
longer inhibit the AR but take on some agonistic activity, or the AR may
become constitutively active, i.e. it no longer needs the presence of
hormone to drive expression of its target genes. Alternatively, the AR
may be bypassed completely and androgen responsive genes may be
activated by a completely different mechanism.
So yes, it's true that antiandrogens have only limited usefulness in
prostate cancer. I don't know if the same is true for healthly patients,
I can't say that I've seen any papers on it.
Chemical castration refers to treatment with oestrogens and leutenising
hormone-releasing hormone (LH-RH) antagonists as well as the
antiandrogens. I'm only guessing but I think this combination will
eventually shrivel your gonads.
I'm not sure about the last question. I don't think cancer cells can
take up the characteristics of the tissue they spread to but don't quote
me on it. Someone please correct me if I'm wrong.
While I'm here I just want to put in my two pence worth. I've been
reading some of the posts in the internet and I'm rather worried
about the atitude some people have towards the use of antiandrogens,
5-AR inhibitors etc. The androgen receptor is a potent transcription
factor vital for development, not just of the sexual organs but a whole
range of other tissues including the brain. Did you know that a mutation
in the AR can cause a neurodegenerative disease? The receptor interacts
with a whole host of other important proteins with very broad ranging
effects. The point I'm trying to make is that knocking out the AR is a
bit severe for treating hairloss. It seems to me like cutting off
your head to cure a headache. The potential for harmful side effects
(infertility, renal and cardiac problems just for starters) is not worth
the benefits. It would seem more sensible to me to try to identify the
androgen responsive genes specifically involved in hair growth/loss and
target drugs towards them. I'm not trying to criticise anyone in this
group, feel free to tell me to piss off if my comments are not welcome,
I'm just worried that some of you guys are doing more harm than good.
