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Hormone
receptors in breast cancer - from bench to bedside
New
drugs being tested to aid breast cancer treatment
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Kaempfero-treated
(A) MCF-7 for  |
Immunostaining
of DMSO-(A) |
Breast
cancer is the most common malignancy in which genesis and
growth have been linked to hormonal factors. Most primary
breast cancers contain
(estrogen receptor alpha) that requires estrogens or estrogenic
activities for tumour growth. Estrogens interact with
and  (estrogen
receptor beta) to modulate the expression of genes involved
in regulating growth, differentiation and survival of cancer
cells.
Since
is the
key player in breast cancer progression, current endocrine
therapies for ER-positive breast tumour are aimed at interrupting
estrogens by oophorectomy or using anti-estrogens. Anti-estrogen
drug Tamoxifen prolongs survival and is used to prevent breast
cancer and treat metastatic ER-positive breast tumours. However,
long-term use of Tamoxifen may cause hormonal resistance and
increases the risk of developing endometrial cancer, thus
limiting its treatment efficacy.
Several
new anti-estrogens and aromatase inhibitors are being tested
for treating breast cancer. New agents with additive effect
or betterefficacy with fewer side-effects are constantly being
evaluated. One such pure antiestrogen ICI 182,780 (ICI) shows
an effect in cells in early testing. NCC scientists and other
investigators have demonstrated that ICI acts as a growth
inhibitor even in the absence of estrogen stimuli. It regulates
gene expression in a direction opposite to that of estrogens
and does not have Tamoxifen's side effects.
Co-administration
of ICI and testosterone causes mammary gland differentiation
and decreases tumour incidence in vivo. Recently, NCC researchers
have shown that kaempferol, a flavonoid, is a growth inhibitor
for ER-positive breast cancer cells. Kaempferol blocks ER
activity by inhibiting
expression, causing
aggregation and inducing degradation of
by a different pathway from that observed for anti-estrogen
ICI and estradiol.
The
efficacy of the hormonal regime and the potential use of a
flavonoid kaempferol to treat breast cancer have to be confirmed
clinically. NCC laboratories are producing new molecules that
can be translated into clinical research to benefit patients.
Dr Hung The Huynh
Principal Investigator
Cellular and Molecular Research
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