Arsenic-based therapy may destroy leukaemia-initiating cells
Scientists have discovered that the toxic element arsenic could be used to attack cells known as leukaemia-initiating cells (LICs), which are thought to drive the formation of leukaemia, and which appear to be resistant to standard cancer therapies.
The researchers found that LICs contain a protein called PML, which helps them to resist treatment by keeping them in a dormant state known as 'quiescence' . By lying dormant, the cells evade existing treatments such as imatinib (Gleevec) and are able to spring into action after a period of time, reinitiating the malignancy.
Intriguingly, high levels of PML are found in a rare type of cancer called acute promyelocytic leukaemia, which responds well to treatment with arsenic. A team of Cancer Research UK scientists recently discovered that arsenic causes these leukaemia cells to attach molecular 'tags' onto PML, telling the cell that the protein should be destroyed.
The discovery that LICs also contain PML opens the door to the potential for arsenic to be used to treat leukaemia, and possibly to target other cancer stem cells. However, the chemical is highly toxic and it is hard to deliver the correct dose without causing side-effects.
The latest findings are published in the journal Nature and senior author Dr Pier Paolo Pandolfi, director of the Cancer Genetics Programme at the Beth Israel Deaconess Medical Centre, commented: "It's actually a very simple concept.
"Ninety percent of existing cancer treatments are anti-proliferative agents - they target the pool of proliferative cells, leaving behind the dormant LICs.
"But in determining that PML serves to guard the LICs that have been left behind, we also discovered that if we knock out PML [ with drugs ], the LICs will lose their braking abilities and run out of gas, thereby committing the fatal error of proliferation - and exposing themselves to the deadly effects of cancer therapies."
The experts are now investigating whether PML plays a similar role in the stem cells of other tissues and in the cancer-initiating cells of solid tumours.
Dr Pandolfi, who is also a professor at Harvard Medical School, added: "If this turns out to be the case, the transient use of As2O3 (an arsenic-based therapy that targets PML) may represent a more global strategy to target CICs in other forms of cancer."