Interview
with Neil Love, MD Breast Cancer Update for Medical Oncologists,
Program 6 2000
Play
Audio Below:
Faslodex
would have been grouped in along with other so-called anti-estrogens,
like tamoxifen. But, in fact, if you look at the spectrum of drugs
that interact with the estrogen receptor, there’s estrogen
on one end of the spectrum, and estrogen seems to stimulate most
genes that are under its control after binding to the estrogen receptor.
Then there are drugs like tamoxifen that stimulate some genes and
inhibit others, depending on the tissue and gene. And then, at the
far other end of the spectrum, there are drugs that seem to have
a predominantly, so-called, pure anti-estrogenic profile. That means
that on every gene that people look at, they’re anti-estrogenic.
They have none of these agonist qualities that tamoxifen does. And
one of these is Faslodex.
It’s
a different structure than the other SERMs, and I’d like to
still think of it as a SERM that has pure antagonist qualities,
as opposed to some other new classification. But other people say
they should be called pure anti-estrogens or pure antagonists.
DL:
I’ve heard estrogen receptor down regulator, too. That’s
another one.
DO:
That’s another one, because it describes one of the differences
in its mechanism of action. But it’s a different structure.
It is a steroid compound. It looks almost exactly like Estradiol
in structure, except it has a side chain that seems to confer its
anti-estrogenic qualities, whereas the other SERMs, like tamoxifen
and Toremifene and these others, are non-steroidal compounds.
So,
Faslodex has a different structure and, in laboratory studies, there
are two or three activation domains on the estrogen receptor protein,
three different areas that seem to be important in activating transcription
of genes. Tamoxifen only blocks one of those, probably the most
important one, but it only blocks one of those, and it leaves open
– the other one is still active. Maybe that gives rise to a
little bit of the agonist qualities of tamoxifen, for instance.
Faslodex, in contrast, blocks all of the activation domains on the
receptor.
Similarities
and distinctions in the mode of action of different classes of antioestrogens
[Review]. Wakeling,
A. E. Endocrine-Related Cancer. 7(1):17-28, 2000 Mar. No abstract
Approaches
targeted to estrogen receptors for treatment of tamoxifen-resistant
breast cancer: A brief overview. Terakawa, N. (Reprint available from: Terakawa N Tottori Univ,
Sch Med, Dept Obstet & Gynecol Yonago Tottori 683 Japan)..
Oncology. 59(Suppl 1):3-4, 2000. No abstract
Treatment
with the pure antiestrogen faslodex (ICI 182780) induces tumor necrosis
factor receptor 1 (TNFR1) expression in MCF-7 breast cancer cells. Smolnikar,
K.; Loffek, S.; Schulz, T.; Michna, H., and Diel, P. (Reprint available
from: Smolnikar K DSHS Cologne, Inst Morphol & Tumor Res Carl
Diem Weg 6 D-50927 Cologne Germany). Breast Cancer Research &
Treatment. 63(3):249-259, 2000 Oct. In process
Symposium
overview: Estrogens and antiestrogens in managing the patient with
breast cancer. Newman,
L. A.; Wood, W. C.; Sellin, R. V.; Morrow, M.; Vogel, C., and Singletary,
S. E (Reprint available from: Singletary SE Univ Texas, MD Anderson
Canc Ctr, Dept Surg Oncol 1515 Holcombe Blvd,Box 106 Houston, TX
77030 USA).. Annals of Surgical Oncology. 7(8):568-574, 2000 Sep.
In process
