New therapy may help combat leukemia
By Natalie Branach
July 18, 2004 9:00 p.m.
For those suffering from leukemia, good news regarding the
possibility of a new treatment option has recently surfaced from
the UCLA Jonsson Cancer Center.
Scientists at the cancer center recently published research
regarding an experimental therapy which could help patients
suffering from chronic myeloid leukemia ““ a slow progressing
cancer that makes the body produce too many cancerous myeloid white
blood cells.
The research led by Neil Shah and fellow researcher Charles
Sawyer ““ both oncologists at the cancer center ““
revolves around developments in the study of a current cancer
therapy drug called Gleevec. This research may lead to a
supplemental drug which could make up for Gleevec’s
shortcomings.
Gleevec is a common drug used to treat leukemia patients and it
is highly effective initially, but as time progresses, its potency
decreases and it becomes more disease resistant, Shah said.
According to a UCLA Health Sciences press release, “about
15 to 20 percent of leukemia patients who take Gleevec become
resistant to the drug and suffer a relapse, leaving them with few
effective treatment options.”
When Gleevec first came on the market in 2001 it slowed the rate
of leukemia progression and the patients had fewer leukemic cells
in their blood and bone marrow than others who were using the
then-current medication.
The goal of Gleevec is to decrease the number of white blood
cells in a patient’s circulation, and then remove the
abnormal cells, according to Gleevec’s Web site.
At first patients responded positively to Gleevec, but the
long-term revealed the decreased potency of the drug, UCLA
researchers said.
An alternative treatment has eluded researchers for quite some
time, but now help may come in the form of a new pill capable of
battling Gleevec’s resistance.
After receiving a developmental compound from pharmaceutical
giant, Bristol-Myers Squibb, the research team discovered the
compound had resistant qualities and it is now undergoing
evaluation.
The results of the study concerning the new investigational
compound were published last Thursday in the peer-reviewed journal
“Science”, and now the compound is in Phase 1
trials.
“The Phase 1 trials are designed to find out the efficacy
of the pill and the appropriate dose,” said Kathy Baum, a
spokeswoman for Bristol-Myers Squibb.
UCLA researchers say that this investigational compound could
add another dimension to the treatment of leukemia.
“In the future, we may be combining therapies that can,
amongst them, override all the resistance mechanisms that allow
cancer to evade individual therapies. In the future, cancer may be
treated similarly to HIV, with a cocktail of drugs,” said
Shah in the press release.
The recent work done on chronic myeloid leukemia by Shah,
Sawyers and others is an accumulation of 20 years of work at
UCLA.
Shah said 20 years ago, in the lab of Owen Whittey, researchers
demonstrated that the underlying genetic abnormality with chronic
myeloid leukemia was a result of an abnormal over productive
protein.
Then, 15 years later researchers began studying an inhibitor
associated with the abnormal protein in the context of clinical
trials, he added.
Today, researchers have found that the abnormal protein has
mutated so that the traditional methods of treatment are less
effective, Shah said.
“In a nutshell, what we here at UCLA have hypothesized is
that to target these mutant forms would be something of clinical
value,” Shah added.
There are two dozen different mutations in the abnormal protein
which have been identified in patients that are resistant to
Gleevec.
The results of the UCLA study show that the investigative
compound is capable of inhibiting the enzymatic activity of 14 out
the 15 Gleevec resistant mutants studied by the UCLA researchers,
Shah said.
“We are hopeful that if it is safely administered to
people it will be of obvious value,” Shah said.
The Phase 1 trials are the first time a compound is administered
to people and is “really designed to evaluate toxicities,
however, occasionally it’s possible to see responses”,
Shah said. “We are encouraged by what we are seeing thus
far.”
Future studies by Shah and Sawyers may also prove to be
beneficial to sufferers of gastrointestinal stromal tumors.
The investigative compound that the UCLA researchers have been
studying came from the labs of Bristol Myers, Baum said.
“The drug was discovered in our labs, and we worked fully
to explore it and do as many clinical trials as we can … now the
UCLA researchers are also conducting trials,” Baum added.
