05 March 2018

A compound that targets STAT5 proteins could help combat acute myeloid leukaemia (AML), an international study has revealed.

STAT5 is a key component of a major cancer-related pathway. Persistent STAT5 activity has been associated with many haematopoietic cancers, and is key to cancer cell survival in leukaemia.  

Now, researchers from Canada, Austria and Hungary say the compound they have discovered targets the oncogenic functions of STAT5 proteins directly and selectively.

Previous attempts to target STAT proteins have been difficult and failed on potency or a lack of specificity.

Writing in Leukemia, the team, led by Professor Richard Moriggl, director of the Ludwig Boltzmann Institute for Cancer Research and professor for functional cancer, describe how they targeted the SH2 domain of STAT5. This is essential for the interactions between STAT proteins that propagate the oncogenic signal.

They have gone on to develop, synthesise and test a new compound that targets the oncogenic functions of STAT5 proteins, they report.

Using a combination of in vitro and in vivo methods, they found that the compound binds directly to STAT5 and disrupts its ability to activate target genes.

First author Bettina Wingelhofer said: “We could show that our novel compound might be a good drug candidate as it impaired the proliferation of patient derived AML cell lines at low concentrations.”

The compound also showed promise in freshly-isolated patient samples. Initial experiments in combinations with established drugs showed that the new compound co-operatively inhibited tumour cell proliferation.

The team says that further research will be necessary to validate the new compound class and establish if it is suitable for clinical trial.


Source: Wingelhofer B, Maurer B, Heyes EC et al. Pharmacologic inhibition of STAT5 in acute myeloid leukaemia. Leukaemia February 2018; doi:10.1038/s41375-017-0005-9

Link: https://www.nature.com/articles/s41375-017-0005-9.pdf


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