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Drug Combo Ramps Up Leukemia Therapy

CancerWise - April 2009

Combining the cancer-fighting drugs NPI-0052 and Zolinza® (vorinostat) appears to be at least five times more effective against leukemia than either agent alone.

Researchers at the Children's Cancer Hospital at M. D. Anderson reported this first-of-its-kind pre-clinical finding in the Jan. 30 online issue of Blood.

NPI-0052 is a proteasome inhibitor. Proteasomes clean out mutated or damaged proteins within cells, promoting cell growth and allowing cancer cells to reproduce rapidly. Proteasome inhibitors block this process, resulting in death of cancer cells.

Vorinostat is a HDAC (histone deacetylase) inhibitor, a type of enzyme that acts on a cancer cell’s genes to make the cell die or stop growing.

Significance of results

Chronic lymphocytic leukemia is the second most common form of leukemia in adults, and acute leukemia is the most common cancer in children.

Background

Previous research showed that NPI-0052 was stronger than other proteasome inhibitors in fighting leukemia cells.

Research methods

In the laboratory, researchers looked at increasing the success of NPI-0052 against leukemia.

"We wanted to improve the effectiveness of NPI-0052, so we started combining it with other agents and found that it was most potent when combined with HDAC inhibitors, " says Joya Chandra, Ph.D., associate professor in the Division of Pediatrics at the Children’s Cancer Hospital and senior author on the study.

Chandra worked with Claudia Miller, a graduate student at M. D. Anderson through The University of Texas Graduate School of Biomedical Sciences at Houston, to analyze the cause of the drugs' synergy by testing them on primary leukemia cells from human samples.

Primary results

For the first time, researchers showed that these anti-cancer drugs work in similar ways.

"We knew the two agents work better together, but we were very surprised to find that they actually act alike," Chandra says. "That's one of the reasons these two agents are so potent against leukemia."

Together, the drugs increased cell death in chronic lymphocytic leukemia fivefold. For acute leukemia, that rate was even greater.

What’s next?

"Combining the two anti-cancer agents may allow clinicians to use lower doses of each drug, which we hope will result in fewer side effects," Chandra says. "For pediatric patients in particular, fewer side effects from treatment could mean a better quality of life in the years ahead."

NPI-0052 is being tested in solid tumor malignancies and recurrent lymphoma in Phase I human clinical trials at M. D. Anderson. A trial to test NPI-0052 and vorinostat in patients is planned.

— Adapted by Mary Brolley from an M. D. Anderson news release

M. D. Anderson resources:

  • Leukemia
  • Children’s Cancer Hospital

© 2014 The University of Texas MD Anderson Cancer Center