The University of Maryland Greenebaum Cancer Center will be the first site in the world to offer leukemia patients a new drug known as MS-275, which is also being studied by the National Cancer Institute for advanced solid tumors.
"This is extremely exciting because MS-275 is a totally new concept in therapy for treating hematologic malignancies," says Judy Karp, M.D., professor of medicine and oncology at the University of Maryland School of Medicine and head of hematologic malignancies at the University of Maryland Greenebaum Cancer Center.
MS-275 is classified as a histone deacetylase inhibitor. "What this drug does is prevent certain molecules from inhibiting the expression of genes involved in the normal process of differentiation and maturation. This drug has the potential to allow leukemia cells to mature appropriately," says Dr. Karp. "By increasing the development of normal, healthy cells, we may be able to stop the proliferation of cancerous leukemia cells."
Leukemia, though not one of the most common cancers, is one of the most rapidly fatal. "At present," says Dr. Karp, "the cure rate for all adult acute leukemias is only 25-30 percent, which means that aggressive therapy with or without bone marrow transplant is not curative for the majority of adults with acute leukemia. New approaches are needed in order to improve the clinical outcome for patients who are currently resistant to standard treatments."
The Greenebaum Cancer Center, known for its work in pioneering some of the earliest studies of new treatment options for leukemia, currently has 10 different clinical trials underway for patients suffering from acute and chronic leukemias.
"It's an exciting time for leukemia research," says Dr. Karp, herself an active researcher for the past three decades. "In the last 10 years, there have been tremendous gains in molecular research that have improved our ability to understand the cellular structure of compounds and genes and to build targeted therapies. Now we can bring that knowledge into clinical studies for patients."
GCC is one of three sites in the country, along with MD Anderson Cancer Institute in Houston, Texas and University of Rochester Cancer Center in Rochester, NY, to offer leukemia patients a drug named SU5416 an "angiogenesis inhibitor" that in the lab has effectively stopped the growth of blood vessels to some cancer tumors. In effect, the drug starves the tumor of needed nutrients and oxygen. The GCC also is one of just three centers nationwide that prescribe minute doses of arsenic trioxide to battle two forms of leukemia when there has been resistance to other therapies or patients have had a relapse. Those types are Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia with blast crisis.
In addition, Karp's team has devised several unique protocols, all involving what are called timed sequential therapies. Timed sequential therapy uses drugs that have already shown promising results, but in new combinations that may be more effective.
"These studies are some of the first of their kind," says Dr. Karp. "All of them are targeting the ability of the cancer cells to survive. We're trying to manipulate cell survival pathways and differentiation pathways in ways that will either enhance the cells' ability to die or to mature and function like a normal cell."
"The abnormality in leukemia is that these cancer cells survive too long. They can't grow up and die. Targeting all the pathways that modulate those events is what we're trying to do."
The trials offer non-traditional chemotherapy agents that reflect recent research discoveries. "This is the result of the last 10-12 years of elegant molecular dissection of the cell," says Dr. Karp.
"We're looking at new combinations of these newer drugs with the more traditional chemotherapies and are hoping to lengthen remissions when they occur. And, in more resistant cases, it may be possible to turn acute leukemia into a chronic disease."
The University of Maryland Greenebaum Cancer Center's Dr. Karp has long been a leader in leukemia research, working alongside Dr. Philip Burke at Johns Hopkins Oncology Center for more than two decades. Together, they discovered time sequential therapy as a treatment option. Dr. Karp joined the Greenebaum Cancer Center four years ago after serving as Special Assistant to the Director of the National Cancer Institute and as Assistant Director, Applied Science, NCI. Dr. Karp is a member of the Leukemia - Lymphoma Society's Medical and Science Affairs Committee and is Vice Chair for clinical research.
For more information about leukemia clinical trials, call the University of Maryland Medical Center's patient referral line at 1-800-492-5538 or visit www.umgcc.org
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