Scientists at the Children's Cancer Hospital at The University of Texas, US, found that a proteasome inhibitor called NPI-0052, could treat acute leukaemia, the first time this class of drugs has been shown effective in this type of cancer. The results were released in the March online issue of the journal Blood.

Millennium Pharmaceuticals' Velcade (bortezomib) is the first and only proteasome inhibitor drug approved by the US Food and Drug Administration (FDA) - in 2003. Although it is effective for treating multiple myeloma and mantle cell lymphoma, it was proven to be ineffective as a single agent against leukaemia in clinical trials.

"NPI-0052 targets the proteasome through different intermediaries and is more potent than bortezomib in leukaemia cells," said Dr Joya Chandra, assistant professor of paediatrics from the Children's Cancer Hospital.

"Therefore we can use less of the drug to inhibit the proteasome."

Proteasome inhibitors limit the function of the proteasome, part of the cell machinery responsible for cleaning up proteins involved in cellular function once they have completed their task. This process promotes cell growth and allows cancer cells to rapidly reproduce and so inhibiting the action can result in the death of malignant cells.

However, due to their broad cellular functions, proteasome inhibitors can have diverse and serious side effects. For example, Velcade can cause reactions such as nausea, vomiting, fatigue, diarrhoea, decreased blood platelets and red blood cells, and numbness or tingling in the extremities. The fact that this potential new drug requires less to work might reduce these side-effects.

The research showed that NPI-0052 inhibits the main enzymatic activity of the proteasome three times more effectively than bortezomib as a single agent. Also, when comparing the two drugs in combination with another anti-cancer agent, a histone deacetylase (HDAC) inhibitor, NPI-0052 works four times as well, according to the scientists.

The investigational compound is also being tested in a Phase I clinical trial on adult patients with solid tumours and recurrent lymphoma. Chandra's group is the first group to be studying the effects of the drug in acute leukaemia models.

"This drug, so far, has shown efficacy in animal models of leukaemia, myeloma and colon cancer, and it has worked to kill multiple myeloma cells resistant to bortezomib," said 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 leukaemia."