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New drug may help to combat leukaemia



DICK AHLSTROM Science Editor

Tue, Nov 03, 2009

THE IRISH Cancer Society has welcomed the discovery by Irish clinical scientists of a powerful new drug that can kill leukaemia cells. The drug works better than those currently in use but also seems to leave healthy tissues untouched.

The work was led by Prof Mark Lawler of Trinity College Dublin and St James’s Hospital and included colleagues from here and also from Italy.

“We were trying to look at new ways to kill cancer cells,” Prof Lawler said yesterday. Details of the research are published this week in the leading journal, Cancer Research .

The team identified a class of drugs that looked promising and then produced 75 related compounds, testing them against leukaemia cells in the laboratory, Prof Lawler said.

They tested the drugs using cells actually recovered from patients rather than standard cancer cell lines, he said. They decided to target chronic lymphocytic leukaemia (CLL), the most common leukaemia in the western world, and one that can sometimes be resistant to current treatments.

The cells were taken with consent from 55 CLL patients, including those who had not responded well to the main drug currently used against the disease, fludarabine.

They found one compound called Pbox-15 had a very strong effect. It readily killed leukaemia cells, including those taken from patients who had shown resistance to therapies already in use, Prof Lawler said.

“It did that better than the drugs we normally use to treat leukaemia,” he said. It was able to kill the cells without harming healthy blood and bone marrow cells, he added.

The researchers are now doing follow-up studies to better understand how the drug works and also to gauge what toxic effects it might have on other healthy tissue types.

Prof Lawler suggested it could take another three to five years before Pbox-15 could be used in human trials. “There is still a long way to go.”

Results are highly promising, however. The drug seems to be able to trigger “apoptosis” or natural cell death in cancer cells, Prof Lawler said. This is important given cancer cells effectively forget how to die and begin to grow out of control.

The drug also seems to attack the cell’s natural architecture, its “cytoskeleton”, he said. This acts like scaffolding that maintains cell shape and protects the cell, but Pbox-15 interferes with this scaffolding.

The drug did not harm normal blood or bone marrow cells, leading the researchers to believe that Pbox-15 targets cell death pathways that are only present in the leukaemia cells and not in normal tissues.

The encouraging findings “emphasise the potential for basic science discoveries to translate to clinical benefit”, stated the Irish Cancer Society’s chief executive, John McCormack.

These findings needed to be brought as quickly as possible “from the laboratory to the bedside, so that they will ultimately benefit patients with this common form of leukaemia”.

Prof Lawler said the discovery came from a “truly collaborative approach”. It included Trinity academics and researchers in Belfast City Hospital and the University of Siena, Italy, involved in chemistry, biochemistry and molecular medicine.

While the Irish Cancer Society was the main funder of the study, the research group also received funding from Science Foundation Ireland, Enterprise Ireland and the HEA’s Programme for Research in third-level institutions.

© 2009 The Irish Times

Owner/SourceThe Irish Times
Date3 Nov 2009

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