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New Hope For Cancer Comes Straight From The Heart
New Hope For Cancer Comes Straight From The Heart
Medical News Today
Article Date: 06 Jan 2009 - 1:00 PST
Digitalis-based drugs like digoxin have been used for
centuries to treat patients with irregular heart rhythms and
heart failure and are still in use today. In the Dec. 16
issue of the Proceedings of the National Academy of Sciences,
researchers at the Johns Hopkins University School of
Medicine now report that this same class of drugs may hold
new promise as a treatment for cancer. This finding emerged
through a search for existing drugs that might slow or stop
cancer progression.
"This is really exciting, to find that a drug already deemed
safe by the FDA also can inhibit a protein crucial for cancer
cell survival," says Gregg L. Semenza, M.D., Ph.D., director
of the vascular program at the Johns Hopkins Institute for
Cell Engineering and a member of the McKusick-Nathans
Institute of Genetic Medicine.
Semenza and his team have long studied the hypoxia-inducible
factor, or HIF-1, protein, which controls genes that help
cells survive under low-oxygen conditions. HIF-1 turns on
genes that grow new blood vessels to help oxygen-starved
cells survive. Regions of low oxygen are common within the
environment of fast-growing solid tumors.
"Oxygen-deprived cancer cells increase their HIF-1 levels to
survive in these unfavorable conditions," says Semenza. "So
turning down or blocking HIF-1 may be key to slowing or
stopping these cells from growing."
The researchers took advantage of the Johns Hopkins Drug
Library, a collection of more than 3,000 drugs already FDA
approved or currently being tested in phase II clinical
trials, assembled by Hopkins pharmacology professor Jun O.
Liu. In this study, the research team tested every drug in
the library for its ability to turn down HIF-1in cancer
cells. The top 20 candidates identified were able to reduce
HIF-1 by more than 88 percent, and more than half of these 20
belong to a class of drugs already commonly used for treating
heart failure, and included digoxin.
The researchers focused on digoxin because of its already
well-established clinical use. They treated prostate cancer
cells grown at normal and low-oxygen levels with digoxin for
three days and counted the number of cells each day. They
found that cells treated with digoxin significantly slowed
their growth, with fewer total cells after three days and
increased numbers of cells that had stopped growing when
compared to untreated cells.
"Many drugs may appear promising when used to treat cancer
cells in a dish in the lab, but may have little or no effect
on tumors in living animals," says Huafeng Zhang, Ph.D., a
research associate in the Department of Oncology and the
Institute for Cell Engineering at Hopkins.
To see if digoxin had the same effect on cancer cells in the
physiological context of a whole animal, the team
administered daily injections of digoxin to mice with tumors.
In untreated mice, tumors were large enough to be felt within
nine days, but in treated mice, tumors could first be felt
only after as long as 15 to 28 days. The team then examined
tumors from the mice and found that HIF-1 levels were lower
than tumors from untreated mice. The team then went on to
show that it is digoxin specifically reducing HIF-1 that
leads to the anti-tumor results they saw.
While Zhang thinks it is possible that drugs like digoxin
could someday be used for treating cancer, she cautions that
a great deal of work remains to be done to understand in
detail how these drugs inhibit HIF-1 and slow or stop tumor
growth. Also, since this class of drugs acts by both
strengthening and slowing down the rhythm of the heart, she
notes that patients can safely tolerate them in only a
limited dosage range a range that is lower than the
concentrations of digoxin used in this study. "We're trying
to kill a tumor," she says, "We don't want to stop a
heart."
Authors of this paper are Huafeng Zhang, David Z. Qian, Yee
Sun Tan, KangAe Lee, Ping Gao, Yunzhao R. Ren, Sergio Rey,
Hans Hammers, Daniel Chang, Roberto Pili, Chi V. Dang, Jun O.
Liu, and Gregg L. Semenza, all of Hopkins.
This work was funded by the Flight Attendant Medical Research
Institute and the Johns Hopkins Institute for Cell
Engineering.
Johns Hopkins Medicine
901 S Bond St.,
Ste. 550 Baltimore MD 21231
United States
http://www.hopkinsmedicine.org
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COMMENT It's great to
see that the medical profession is looking at such drugs in cancer
therapy. It is particularly good to see because in cancers most heart
drugs were shown in the 1980s and '90s to be far superior and much
more effective than the usual run of conventional and largely useless
chemotherapy drugs.
You might be interested in an article
about heart drugs in cancer which I wrote (here) about eight years ago. One thing
to note is that the digoxin in the Medical News Today
report, was found to be not as effective as its predecessor,
digitoxin. But, I suppose, it is a hopeful sign and a move in the
right direction.
Last updated 6 January 2009
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