Iron-reducing drug starves acute leukaemia cells then kills them

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New research has found a drug that reduces iron in acute myeloid leukaemia cells, effectively starving them to death. The drug ironomycin has been studied by scientists at Melbourne's Peter MacCallum Cancer Centre and two French Cancer Comprehensive Centres: Institut Paoli-Calmettes in Marseilles, and the Institut Curie in Paris.

This new research was published in Cancer Discovery, a journal of the American Association for Cancer Research.

The researchers have also shown in a laboratory setting, that when ironomycin is given in combination with the established anti-cancer drug venetoclax, the effects of both drugs are amplified.

Venetoclax has now been listed on the Pharmaceutical Benefits Scheme for the treatment of acute myeloid leukaemia (AML).

Peter Mac's Professor Mark Dawson, a senior author on the paper, said that together, ironomycin and venetoclax would provide another powerful weapon in the fight against cancer.

"Given our experience with using venetoclax to treat acute myeloid leukaemia, we are learning many of the ways that our patient's leukaemia cells can become resistant to it," Professor Dawson said.

"But by using it in combination with ironomycin, this preliminary work suggests that you get a much greater effect than by using venetoclax alone, and ironomycin overcomes some of the known deficiencies of venetoclax because they work by different pathways."

Ironomycin was originally created at the Institut Curie, and has been shown to kill breast cancer stem cells in preclinical models. Through this research, we now know it works by reducing the availability of iron in the mitochondria of cells. The mitochondria are often referred to as the powerhouse of the cell, because they are a major hub for cellular metabolism.

Cancer cells needs lots of energy, which is why disrupting cancer metabolism provides such an exciting opportunity for new therapies.

While the cancer cells are disrupted by ironomycin causing them to die, normal healthy cells are less dependent on one metabolic pathway and can switch to other pathways for energy production and continue living.

Institut Curie's Professor Raphael Rodriguez, a senior author on the paper, said that this newly discovered mechanism of ironomycin in AML also provides us with an opportunity to better understand how manipulating levels of iron within specific compartments triggers cancer cell death. This knowledge may lead to a new class of anti-cancer drugs like ironomycin.

The paper's first author, Dr Sylvain Garciaz, formerly of Peter Mac but now at the Institut Paoli-Calmettes, said: "This work done under Mark Dawson's supervision was an incredibly collaborative study involving both Australian and French teams. The next challenge we face going forward is to understand how best to use the drug in clinical practice, in particular for patients with acute myeloid leukemia."