RC
: The peoxisome proliferator-activated receptors
(what a mouthful! The acronym is PPAR) are members
of a superfamily of nuclear hormone receptors
that play a diverse regulatory role on metabolism
including the regulation of lipid and sugar
metabolism. Activation of PPAR receptors elicit
anti-inflammatory and anti-cancer effects (via
apoptosis and antiangiogenesis as well as direct
antiproliferation). Of the isoforms of PPAR
family so far identified, the PPAR-gamma isoform
is especially promising as a therapeutic possibility
in cancer. PPAR-gamma agonist are now in clinical
use as anti-diabetic drugs (e.g. rosiglitazone)
because activation of PPAR-gamma lowers serum
glucose in diabetics. In vitro and animal* studies
have documented the anticancer effects of PPAR-gamma
agonists in a broad array of tumors including
prostate*, thyroid*, gastric, colon*, pancreas,
liver, breast*, lung, brain and neuroblastoma.
To date, clinical trials with rosiglitazone
have shown efficacy in PPAR agonist treatment
with prostate
cancer and
liposarcoma. Results are particularly
impressive in prostate cancer cases wher troglitazone
800mg a day stabilized PSA in patients with
advanced prostate cancer. A nice review of PPAR
and cancer was recently published in Lancet
Oncology.
We have been using a cocktail
of cox-2 antagonist, PPAR gamma
agonist and statins where clinically
appropriate to treat various cancers and have
noted general tolerability of this approach
even in non-diabetics. From our experience,
it is doubtful if PPAR gamma agonists given
alone has much efficacy in treating established
cancer, but a cocktail approach with other antiangiogenic
and apoptosis
agents can be especially useful
in chemoprevention (See
Ref) and secodary prevention or
adjunct treatment of certain cancers. It has
already been proposed as a viable preventative
approach in prostate (See Ref)
as well as breast (See Ref)
cancer.
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