Abbott Experimental Drug Kills Leukemia Cells
Posted on: Monday, 20 November 2006, 09:01 CST
Researchers at the University of Texas MD Anderson Cancer Center have found that Abbott Laboratories' experimental drug ABT-737 can destroy acute myeloid leukemia cells.
The drug was powerful in its own right, the researchers say, but they found that some acute myeloid (AML) cells were themselves resistant to ABT-737, so they added another drug that knocked out this secondary resistance. Together, these agents may provide a powerful therapy against AML, and could form the basis of a new way to treat the cancer, say the scientists.
"The combination of these two experimental drugs provides the highest synergistic action I have ever seen against acute myeloid leukemia cells," said Michael Andreeff, professor in the center's departments of stem cell transplantation and leukemia.
In this study, researchers found that ABT-737 "potently" kills AML cell lines as well as blast cells taken from AML patients. ABT-737 targets BCL-2, which is a cell 'survival' protein that is over-expressed in many types of cancer. This protein prevents a cell from committing apoptosis (cell death) by latching on to other BCL-2 family member proteins, rendering them ineffective.
However, AML cells in which another a protein known as MCL-1 is over expressed did not die, which makes this protein a "resistance factor" to ABT-737 and to standard chemotherapy, Mr Andreeff said.
The researchers added an experimental drug, a MAP-kinase inhibitor, to knock down MCL-1 expression, and found that this inhibitor also worked to inhibit cells in which BCL-2 is phosphorylated, which can switch a protein on or off. "ABT-737 had diminished effects against cells with phosphorylated BCL-2, which was restored by combination with a MAPK inhibitor," Mr Andreeff said.
MD Anderson Cancer Center said that the next step is to test ABT-737 in patients with leukemias.
Source: Datamonitor
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