10 January 2019

Progress is being made towards a new combination therapy for chronic lymphocytic leukaemia (CLL), British researchers have announced.

Dr Alison Michie and her team from the University of Glasgow looked at the potential for using ibrutinib together with a new drug called AZD8055.

Ibrutinib is effective at improving survival for high-risk CLL patients, but patients can develop resistance to the drug. To reduce the rate of drug resistance, researchers have been examining new combination of treatments that attack the disease in multiple ways.

The new drug, AZD8055, blocks the activity of mTORC1 and mTORC2, which regulates cell growth and activity. Testing in patient samples and mice, Dr Michie’s team investigated whether this drug alone, or in combination with ibrutinib, could effectively kill leukaemia cells.

Results were published in the journal Clinical Cancer Research on 17th December 2018. The team write that the new drug "significantly reduced chronic lymphocytic leukaemia cell survival in vitro, preferentially targeting poor prognostic subsets and overcoming survival advantages."

They add that this positive effect "was further significantly enhanced on combining the new drug with ibrutinib" and that the combination showed promise as a future CLL therapy.

Dr Michie said: "Reducing the ability of chronic lymphocytic leukaemia cells to survive is key to interrupting disease progression.

“Combining mTOR inhibition with a drug called ibrutinib, which is currently being used in the clinic to treat high-risk chronic lymphocytic leukaemia patients, enhances the activation of FOXO1, a protein that can promote cell death, in a preclinical model.

"Our findings are important because they could demonstrate a potential new therapeutic approach for treating patients with high-risk chronic lymphocytic leukaemia.”

Source: Cosimo, E., Tarafdar, A., Moles, M.W., Holroyd, A.K., Malik, N., Catherwood, M.A., Hay, J., Dunn, K.M., Macdonald, A.M., Guichard, S.M., O'Rourke, D.M., Leach, M.T., Sansom, O.J., Cosulich, S.C., McCaig, A.M., Michie, A.M. (2018), “AKT/mTORC2 inhibition activates FOXO1 function in CLL cells reducing B cell receptor-mediated survival”, Clinical Cancer Research, available at doi: 10.1158/1078-0432.CCR-18-2036


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