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Haematological cancer

Send in the decoys, STAT!

Nature Reviews Clinical Oncology volume 13, page 136 (2016)Cite this article

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STAT3 is a transcription factor involved in cell survival and immunosuppression, and is implicated in acute myeloid leukaemia (AML). Efforts to inhibit STAT3 have been limited by the inherent difficulties in targeting transcription factors lacking catalytic activity; however, Marcin Kortylewski and co-workers have developed a cell-selective STAT3 decoy oligodeoxynucleotide (dODN) that overcomes these challenges.

The dODN comprises STAT3-binding and CpG DNA sequences. CpG motifs are recognized by Toll-like receptor 9 (TLR9) enabling targeting of the dODN to myeloid cells that express this receptor, including AML cells, tumour-associated macrophages, and myeloid-derived suppressor cells (MDSCs). Indeed, the dODN efficiently penetrated all AML cell types (including leukaemic stem/progenitor cells), sequestered STAT3, inhibited its transcriptional activity, and caused disease regression in mouse models of human AML.

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References

  1. Zhang, Q. et al. Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia. Blood http://dx.doi.org/10.1182/blood-2015-08-665604 (2016)

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Authors
  1. David Killock
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Killock, D. Send in the decoys, STAT!. Nat Rev Clin Oncol 13, 136 (2016). https://doi.org/10.1038/nrclinonc.2016.17

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  • DOI: https://doi.org/10.1038/nrclinonc.2016.17

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