Breast Cancer
ironjustice
Bone-Building Drugs May Cut Breast Cancer Risk
Women Who Take Bisphosphonates About One-Third Less Likely to Develop
Cancer
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New Anti-cancer Drug: 200 Times More Active In Killing Tumor Cells
ScienceDaily (Mar. 26, 2009) — A team of 24 researchers from the
U.S.,
Europe, Taiwan and Japan and led by University of Illinois scientists
has engineered a new anti-cancer agent that is about 200 times more
active in killing tumor cells than similar drugs used in recent
clinical trials.
The study appears this week in the Journal of the American Chemical
Society.
The new agent belongs to a class of drugs called bisphosphonates.
These compounds were originally developed to treat osteoporosis and
other bone diseases, but were recently found to also have potent
anti-
cancer and immune boosting properties.
Drug developers have tried for years to design drugs to inhibit cell
survival pathways in tumor cells, focusing on a protein called Ras
since nearly a third of all human cancers involve a mutation in the
Ras gene that causes cell signaling to go awry. These efforts have
met
with limited success.
Bisphosphonates act on other enzymes, called FPPS and GGPPS, which
are
upstream of Ras in the cell survival pathway. Inhibiting these
enzymes
appears to be a more effective strategy for killing cancer cells.
When used in combination with hormone therapy in a recent clinical
trial, the bisphosphonate drug zoledronate significantly reduced the
recurrence of breast cancer in premenopausal women with estrogen-
receptor-positive breast cancer. Similar results were reported
previously for hormone-refractory prostate cancer.
But zoledronate quickly binds to bone, reducing its efficacy in other
tissues.
"We're trying to develop bisphosphonates that will be very active but
won't bind to the bone, because if they bind to the bone they're not
going to go to breast, lung or other tissues," said University of
Illinois chemistry professor Eric Oldfield, who led the new study.
Oldfield's team also wanted to design a compound that would inhibit
multiple enzymes in the tumor cell survival pathway, rather than just
one, an approach analogous to the use of multi-kinase inhibitors in
cancer therapy.
Andrew Wang, of Academia Sinica, Taipei, and Illinois chemist Rong
Cao
began by producing crystallographic structures of the target enzymes
and drug candidates, allowing the researchers to identify those
features that would enhance the drugs' ability to bind to the
enzymes.
Using this and other chemical data, Illinois chemistry department
research scientist Yonghui Zhang engineered new bisphosphonate
compounds that bound tightly to multiple enzyme targets, but not to
bone.
One of the new compounds, called BPH-715, proved to be especially
potent in cell culture and effectively inhibited tumor cell growth
and
invasiveness.
Tadahiko Kubo, of Hiroshima University, then found that BPH-715 also
killed tumor cells in mice. And Socrates Papapoulos, of Leiden
University, the Netherlands, showed that the compound had a very low
chemical affinity for bone.
In humans, compounds like BPH-715 and zoledronate have an added
benefit in fighting cancer: They spur the proliferation of immune
cells called gamma delta T-cells, which aid in killing tumor cells.
"The new drugs are about 200 times more effective than the drugs used
in recent clinical trials at killing tumor cells and in activating
gamma delta T-cells to kill tumor cells," Oldfield said. "They also
prevent tumor progression in mice much better than do existing
bisphosphonate molecules."
Journal reference:
Zhang et al. Lipophilic Bisphosphonates as Dual Farnesyl/
Geranylgeranyl Diphosphate Synthase Inhibitors: An X-ray and NMR
Investigation. Journal of the American Chemical Society, 2009;
090323145321030 DOI: 10.1021/ja808285e
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IP6 is phytic acid which is phytate.
It is a natural bisphosphonate found in any health food store.
It is made from 'bran' .. from 'chaff' / husk of your grains.
It is a free bisphosphonate found in your foods.
Peas are especially high in this bisphosphonate / phytate.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk