Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have found that a novel targeted therapy effectively treats acute leukemia in animal models by preventing cancer cells from being purged of damaged proteins.
In the March online issue of the journal Blood, investigators reported that the new proteasome inhibitor, NPI-0052, not only successfully kills leukemia cells, but also shows greater efficacy than its predecessor bortezomib when combined with other agents in animal models.
According to researchers, proteasomes clean out mutated or damaged proteins within cells, which promotes cell growth and allows cancer cells to rapidly reproduce. Proteasome inhibitors block this process, resulting in apoptosis, or cell death, of the malignant cells.
Bortezomib is the first and only FDA-approved proteasome inhibitor. Although it is effective for treating multiple myeloma and mantle cell lymphoma, it was proven to be ineffective as a single agent against leukemia in clinical trials. NPI-0052 varies from bortezomib in ways that researchers at M. D. Anderson hope will make NPI-0052 effective in a human clinical trial.
"NPI-0052 targets the proteasome through different intermediaries and is more potent than bortezomib in leukemia cells," says senior author Joya Chandra, Ph.D., assistant professor of pediatrics from the Children's Cancer Hospital at M. D. Anderson. "Therefore we can use less of the drug to inhibit the proteasome."