Interview
with Neil Love, MD Breast Cancer Update for Medical Oncologists,
Program 6 2000
Play
Audio Below:
Faslodex-bound
receptor is degraded, so that somehow when Faslodex binds that receptor,
it induces degradation pathways. What people find is that when you
measure the receptor, the estrogen receptor, over time, after treating
an animal or a cell or a person with Faslodex, the amount of receptor
in a cell declines. There have been studies showing that the receptor
winds up in lysosomes and gets degraded. All of our endocrine therapies
target the estrogen receptor. That’s the whole thing. You want
to block the estrogen receptor function or you want to get rid of
the ligand, so-called estrogen that activates the receptor –
that’s how ovariectomy and aromatase inhibitors work. But,
if you really want to design the best therapy, it would be to get
rid of the receptor. Then you’d have no effect of estrogen
at all. And that’s what Faslodex does, it reduces the level
of the receptor. In some cases, you can’t measure it after
exposure to Faslodex. And so for those reasons, those different
mechanisms of action, one could hypothesize, first, that Faslodex
would be a more potent anti-tumor drug. It doesn’t have any
of this agonist activity, blocks all the transcription domains,
and it gets rid of the receptor. It might be more active. And secondly,
it might work even in tumors that are resistant to tamoxifen, particularly
those tumors that the resistance is due to tamoxifen-stimulated
growth.
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
