Novel strategy under study for aggressiv...(aggressive leukemia occurs most commonly...),Health

If you just target FLT-3 with an inhibitor of its activity, that would not be enough, says Dr. Bhalla. If you combine it with something that also depletes its levels, that would be better. But if you deplete its levels, inhibit its activity and combine it with another leukemia cell death-inducing agent, it would be even better, says Dr. Bhalla, who believes the laboratory work will evolve into a strategy that can be used effectively in the clinics, maybe even before the laboratory work is done.

A big plus is that several drugs that do each of these things already are being studied in patients. However, combined effects of these drugs have not been fully studied against leukemia cells, and the drugs just havent been used together in patients with leukemia.

For example, one of the histone deacetylase inhibitors Dr. Bhalla will study in the lab, LBH589, developed by Novartis Corp., hes also studying in an early clinical trial for patients with leukemia and lymphoma for whom standard therapies have failed. Several FLT-3 kinase inhibitors are under study for a variety of cancers and MCG will soon join one of those studies for leukemia. Apo2L/TRAIL, developed by Genetech, is under study in a variety of solid tumors and leukemia. TRAIL activates on leukemic cells the same death-inducing stimulus immune cells use to kill cancer cells. Its a normal mechanism of killing offending cells, says Dr. Bhalla.

We have designed combinations of agents that we will be studying in mouse models and against patient-derived leukemia cells. This grant doesnt fund a clinical trial, but it allows us to take patient samples and study them in vitro to further define why this gene confers poor survival and what combinations can work against it, says Dr. Bhalla. He notes that since the drugs are new and have not previously been
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