Novel drug preventing protein recycling shows potential for treating leukemia

April 19, 2007

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."

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. Chandra's group is the first group to be studying 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," says Chandra. "As a result of our research, we're looking at the feasibility of combining NPI-0052 with HDAC inhibitors in the future to treat leukemia."

Source: University of Texas M. D. Anderson Cancer Center

Explore further: Drug-encapsulating nanoparticle to measure how anticancer chemotherapy formulations enter cells

Related Stories

New technology maps human genome in days

May 5, 2015

The two 3-by-1-inch glass chips held the unfathomable amount of genetic information contained in 16 human genomes. Last week, a technician placed the chips - called flow cells - in a new genetic sequencing machine at the ...

A breakthrough in nanotoxicology

February 18, 2015

Whereas resistance to antibiotics complicates certain treatments, antimicrobial silver nanoparticles (AgNP) are gaining popularity for medical use. These particles are toxic for certain bacteria, but what about for humans? ...

Recommended for you

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

Quantum Theory May Explain Wishful Thinking

April 14, 2009

(PhysOrg.com) -- Humans don’t always make the most rational decisions. As studies have shown, even when logic and reasoning point in one direction, sometimes we chose the opposite route, motivated by personal bias or simply ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.