Acute Leukemia Successfully Treated in Animal Models

Proteasome inhibitors block this process, resulting in apoptosis, or cell death, of the malignant cells.

Researchers from the Children's Cancer Hospital at The University of Texas M.D. Anderson Cancer Center (Houston, TX, USA) found 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. Their findings appeared in the March 2007 online issue of the journal Blood

Bortezomib is the first and only US Food and Drug Administration (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, said 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.

NPI-0052 inhibits the main enzymatic activity of the proteasome three times more effectively than bortezomib as a single agent. When combined with a histone deacetylase (HDAC) inhibitor, another anti-cancer agent, NPI-0052 achieves four-fold greater synergistic effects than bortezomib.

M.D. Anderson currently has a phase I clinical trial led by principal investigator Razelle Kurzrock, M.D., to test NPI-0052 on adult patients with solid tumor malignancies and recurrent lymphoma. Dr. Chandra's group is the first group to study the effects of the drug in acute leukemia models.

This drug, so far, has shown efficacy in animal models of leukemia, myeloma, and colon cancer, and it has worked to kill multiple myeloma cells resistant to bortezomib, said Dr. Chandra. As a result of our research, we're looking at the feasibility of combining NPI-0052 with histone deacetylase (HDAC) inhibitors in the future to treat leukemia.


Related Links:
University of Texas M.D. Anderson Cancer Center