21 May 2020
New therapeutic targets for an old drug
Published online 14 August 2016
Ibrutinib targets microRNAs that reduce the expression level of tumour suppressor genes.
Scientists have revealed a new mechanism of action of an anti-leukaemic drug used mainly against chronic lymphocytic leukaemia (CLL) called ibrutinib1.
The international research team, including researchers from Mansoura University, Egypt, has identified a panel of miRNAs that are targeted by ibrutinib in CLL patients.
MicroRNAs (miRNAs) are short sequences of RNA nucleotides that regulate the protein levels of their target genes. As a result, identifying the miRNAs mediating the unbalance between the cancerous cells' increased proliferation and decreased death rates, by regulating tumour suppressor or promoting genes, can lead to revealing fresh therapeutic targets.
In this study, the scientists compared samples from CLL patients before and after ibrutinib treatment, and found that a panel of miRNAs was significantly downregulated as a consequence of said treatment.
This worked across signaling pathways that became disrupted not only in liquid tumours as CLL, but also in solid tumours, such as stomach, pancreas and breast cancer.
The results were confirmed to be specific to ibrutinib.
"These findings expand our knowledge of the roles miRNA play in the biology of CLL, and may contribute to the advancement of therapeutic target development in the treatment of CLL and other malignancies," says Katherine Calvo, from the Department of Laboratory Medicine at the National Institutes of Health, USA.
- Saleh L. M. et al. Ibrutinib downregulates a subset of miRNA leading to upregulation of tumor suppressors and inhibition of cell proliferation in chronic lymphocytic leukemia. Leukemia. http://dx.doi.org/10.1038/leu.2016.181 (2016).