Drug Has Ability To Cure Type Of Leukemia
Source: University of California, Irvine
Date: October 3, 2007
Science Daily — In people with chronic myeloid leukemia (CML), the
drug Imatinib has been shown to drive cancer into remission, but the
disease often returns when treatment is stopped. New research by UC
Irvine scientists indicates that Imatinib could cure CML under
certain circumstances if it is taken over a long enough period of
time.
Mathematician Natalia Komarova and biologist Dominik Wodarz also
developed a tool that eventually could help doctors determine which
combination of drugs would be most beneficial to a CML patient, and
they determined why, in some cases, Imatinib does not block cancer
growth.
CML is a quick-progressing cancer that starts in the bone marrow and
moves into the blood. The disease proceeds in three stages, the last
one characterized by patient survival of only a few months. In 2007,
an estimated 4,570 people in the United States will develop CML, and
490 people will die from it, according to the National Cancer
Institute, a division of the U.S. National Institutes of Health.
The drug Imatinib is a promising cancer treatment because it has few
side effects, and it specifically targets cancer cells. In their
study, the UCI scientists focused on Imatinib and the behavior of
cancerous stem cells. Just as normal stem cells maintain organs and a
functioning body, cancer stem cells are thought to maintain cancer
growth and are tough to kill with treatment.
Many scientists believe that Imatinib can kill regular cancer cells
but not stem cells. When treatment ends, the remaining stem cells can
produce more cancer cells, thus exacerbating the disease. According
to this view, there is no hope to cure CML.
The UCI scientists, however, believe Imatinib can kill cancerous stem
cells but not when the stem cells temporarily stop dividing, a state
known as quiescence. All cancerous stem cells have the ability to
enter the quiescent state. Evidence indicates that when such sleeping
stem cells wake up, Imatinib can kill them.
In their paper, the scientists present a mathematical formula that
can calculate how long it would take to kill all of the stem cells
and cure the cancer. This length of time -- which could be different
for each patient -- is based on how often the cancerous stem cells
fall asleep and how quickly they wake up. Once the scientists can
test their theory with patients, they will be able to determine how
long the cure might take.
"There is evidence that a complete cure is possible. Several patients
have been reported to have no symptoms after two months without
therapy, which is thought to suggest a complete cure," Komarova
said. "This evidence supports our theory. Basically, one has to be on
therapy long enough for all of the stem cells to wake up and be
killed by the drug."
In addition to sleeping stem cells, another barrier to eradication by
Imatinib is that cancer cells can mutate to become unresponsive to
certain drugs. Conventional thought is that if sleeping stem cells
prolong a cure, other cancer cells will have ample time to mutate and
become drug resistant.
The UCI scientists, however, have proved this theory wrong. Their
calculations show that mutant cells develop early on, in many cases
before the patients know they are sick, and do not develop during the
treatment process. Using mathematics, they developed a way to
calculate the probability that certain mutations exist in a patient.
Based on this, one can determine what course of treatment should be
used to overcome the resistance.
"The model requires the number of cancer cells that exist, how fast
the cells divide and die, and how fast they go to sleep and wake up,"
Wodarz said. "Once you have those numbers, you can determine how many
drugs to use in combination to make sure drug resistant mutants do
not become problems."
The results of their study will appear Oct. 3 in the journal Public
Library of Science One.
This research was supported in part by a National Institutes of
Health grant and a Sloan Fellowship.
Note: This story has been adapted from material provided by
University of California, Irvine.
http://www.scienced
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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