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26 June 2017


Scientists have investigated ways in which the body supports lymphoma cells and allows resistance to occur.

Dr Eduardo Sotomayor and colleagues at the George Washington University Cancer Center, Washington, USA, looked at why many patients with mantle cell lymphoma develop resistance to the medication ibrutinib.

Ibrutinib shuts down the bruton tyrosine kinase pathway, which threatens the survival of lymphoma cells. But when this happens, the lymphoma cells switch to another pathway for their survival. This new pathway is called PI3K-AKT-mTOR.

Sometimes the lymphoma cells become even more aggressive once they have begun using this alternative pathway, the team report. Full details of their findings were published in Nature Communications recently.

The authors say that inhibiting all of the possible pathways could lead to ibrutinib becoming more effective, less likely to trigger resistance, and suitable for a wider group of patients.

Dr Sotomayor stated: 'Not all patients will react to a drug in the same way. Some will take it and no longer show symptoms of lymphoma. In others, they may not show a response to the treatment at all, and in other, after an initial response to treatment, the lymphoma may come back more aggressive than before. What we wanted to understand is: How can we make this treatment work for everyone?

'Mantle cell lymphoma cells depend on strong interactions with the microenvironment for progression. Rather than focus on the cells themselves, our team was concerned about understanding the microenvironment where the cells thrive and find protection.

'We need to look at the tumour cells in the context of the microenvironment to understand how they build up resistance.'

Source: Zhao, X. et al. Unification of de novo and Acquired Ibrutinib Resistance in Mantle Cell Lymphoma. Nature Communications 18 April 2017; doi: 10.1038/ncomms14920

Link: https://www.ncbi.nlm.nih.gov/pubmed/28416797


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